Clinical trial NCT04826094
Conditions: HIV Infections
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2021-03-15; Completion date: 2024-02-13
Enrollment: 143 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a study of HIV vaccines. A vaccine is a medical product given to prevent certain diseases. The vaccine may educate the body to form a defensive response to try to prevent the disease from the beginning, or preventing it from taking hold of the body. This defensive response is called the immune response. The experimental vaccines in this study are Env-C Plasmid DNA and HIV Env gp145 C690 protein, given with different adjuvants. An adjuvant is a substance added to vaccines that can help make the vaccine more effective by improving the immune response, or by causing the immune response to last longer than it would without the adjuvant. The adjuvants are mixed with the vaccines and injected into muscle or placed on top of the skin. The HIV vaccines contain a piece of genetic material or a protein copied drom the HIV virus cover (Env), but they do not contain the virus itself. The vaccines cannot cause HIV infection or Acquired Immune Deficiency Syndrome (AIDS).

The purpose of this study is to find out if the study vaccines with adjuvants cause side effects and are tolerable, whether humans respond (develop immune responses) to the vaccines, and how ling the effects of the study vaccines last. The study will also compare the effects of the study vaccines with adjuvants and adjuvant patch to those of placebo injections and placebo patch. The placebo will consist of saline (sterile saltwater) and will look like study vaccines, be given in the same way, but will have no active vaccine or adjuvant in it. A total of 126 participants will take part in the study and each will have up to 26 clinic visits and will be followed-up for a total of 108 weeks.

Detailed description:
Antibodies are the most commonly recognized correlate of vaccine protection from infection; however the possible protective HIV antibody levels, which were induced by the modestly protective RV144 vaccine regimen with alum, rapidly decayed. Potentially, a novel, highly selective adjuvant combined with the correctly sequenced HIV antigen could slow antibody decay, increase antibody magnitude and induce antibodies of appropriate functional response.

RV460 is an exploratory study that will assess the safety, tolerability, and immunogenicity of a vaccine regimen consisting of priming with an Env-C Plasmid DNA vaccine (with or without novel adjuvants) when given with or without adjuvanted HIV Env gp145 C.6980 protein vaccine and boosting with adjuvanted gp145 C.6980 protein with or without the gp120 DNA vaccine. The study will be carried out in Kericho, Kenya. 126 healthy adults will ben enrolled. Participants will be randomized into one of seven groups which have 15/3 vaccine/placebo recipients per group. Each participant will receive six injections (prim at week 0, 4, 12; boost at week 20, 32 and 56) and will be followed-up for a total of 108 weeks.

Arms: arm 1: 3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56 arm 2: 3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56 arm 3: 3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56 arm 4: 3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56 arm 5: 3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56 arm 6: 3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56 arm 7: 3 doses of prime vaccination at weeks 0, 4, 12 followed by 3 doses of boost vaccination at weeks 20, 32, 56 arm 8: Pooled placebo arm.
Interventions: intervention 1: Env-C Plasmid DNA intervention 2: HIV Env gp145 C.6980 protein intervention 3: Rehydragel® intervention 4: ALF43 intervention 5: dmLT intervention 6: Placebo (IM) intervention 7: Placebo (TCl)
Intervention descriptions: intervention 1: 2 mg per dose. Administered by intramuscular injection. intervention 2: 100 µg per dose. Administered by intramuscular injection. intervention 3: Adjuvant. Aluminum hydroxide fluid gel. 500 µg per dose. Administered by intramuscular injection. intervention 4: Adjuvant. Army Liposome Formulation-43% Cholesterol. 200 µg per dose. Administered by intramuscular injection. intervention 5: Adjuvant. Recombinant double mutant Escherichia coli heat labile toxin. 50 µg per dose. Transcutaneous application (needle-free skin patch). 1 mL diluted dmLT added to gauze pad at site of injection. intervention 6: 0.9% sodium chloride (sterile saline). Administered by intramuscular injection. intervention 7: Transcutaneous application (needle-free skin patch). 0.9% sodium chloride (sterile saline) added to gauze pad at site of injection.

Protocol documents:
Prot_ICF_000.pdf: 
RV460 / WRAIR #2672 
 
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Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
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PROTOCOL RV460 
A Randomized, Double-Blind Phase 1 Trial to Evaluate the Safety and Immunogenicity of 
Priming with Env-C Plasmid DNA Vaccine Alone, with Different Adjuvants, or with an 
Adjuvanted HIV Env gp145 C.6980 Protein Vaccine and Boosting with the Adjuvanted 
HIV Env gp145 C.6980 Protein Vaccine with or without the Env-C Plasmid DNA Vaccine 
in Healthy HIV Uninfected Adults in Kenya 
Short Title of Study:  
Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
Study Conducted By: 
United States Army Medical Research Directorate-Africa (USAMRD-A), Clinical Research 
Centre, Kericho, Kenya 
IND Sponsored By: 
National Institute of Allergy and Infectious Diseases (NIAID) 
Division of AIDS (DAIDS) 
Bethesda, Maryland 
 
IND Number: 21093 
 
Funding Agencies: 
Cooperative Agreement between Congressionally Directed Medical Research Programs 
(CDMRP)--United States Army Medical Research Acquisition Activity (USAMRAA) and 
the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF); 
Proposal PR140267, Award PI: Gary Matyas, Prime Award W81XWH-15-2-0079  
 
Principal Investigator: 
Josphat Kosgei MBChB, MSc 
 
DoD Research Monitor: 
Jonah Maswai, MBChB, MPH 
 
DAIDS Medical Officer: 
Laura Polakowski, MD, MSPH 
 
 
NCT04826094


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PROTOCOL TEAM 
PROTOCOL CHAIR  
 
 
 
Christina Polyak, MD 
U.S. Military HIV Research Program (MHRP)/ 
Walter Reed Army Institute of Research (WRAIR) 
6720A Rockledge Drive 
Bethesda, MD. USA 20817 
Phone: 301-500-3688 
Email: cpolyak@hivresearch.org 
 
PROTOCOL CO-CHAIR 
Sandhya Vasan, MD 
U.S. Military HIV Research Program (MHRP)/ 
Walter Reed Army Institute of Research (WRAIR) 
6720A Rockledge Drive 
Bethesda, MD. USA 20817 
Phone: 301-500-3622 
Email: svasan@hivresearch.org 
 
PRINCIPAL INVESTIGATOR 
Josphat Kosgei, MBChB, MSc 
 
 
Kenya Medical Research Institute/US Medical Research Directorate-Africa 
P.O. Box 1357-20200 Kericho, Kenya. 
Phone: +25452-20-30686; Mobile: +254 729 110 122 Fax +254-52-20-30546 
Email: josphat.kosgei@usamru-k.org 
 
ASSOCIATE INVESTIGATORS 
Merlin Robb, MD 
U.S. Military HIV Research Program (MHRP)/ 
Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) 
6720A Rockledge Drive 
Bethesda, MD. USA 20817 
Phone: 301-500-8302 
Email: mrobb@hivresearch.org 
 
SITE ASSOCIATE INVESTIGATORS 
Fredrick Sawe, M.B.Ch.B., M.MED. 
Kenya Medical Research Institute/US Army Medical Research Directorate-Africa 
P.O. Box 1357-20200 Kericho, Kenya. 
Phone: +25452-20-30686; Mobile: +254 703 247 902 Fax +254-52-20-30546 
Email: fredrick.sawe@usamru-k.org 
 
Deborah Langat, MBChB, MSc 
Kenya Medical Research Institute/US Army Medical Research Directorate-Africa 
P.O. Box 1357-20200 Kericho, Kenya. 


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Phone: +25452-20-30686; Mobile: +254 714 059596 Fax +254-52-20-30546 
Email: deborah.langat@usamru-k.org 
 
Lucy Koech, MBChB 
Kenya Medical Research Institute/US Army Medical Research Directorate-Africa 
P.O. Box 1357-20200 Kericho, Kenya. 
Phone: +25452-20-30686; Mobile: +254 719 193 275 Fax +254-52-20-30546 
Email: lucy.koech@usamru-k.org 
 
Faith Riziki, BPharm, MSc 
Pharmacist of Record 
Kenya Medical Research Institute/US Army Medical Research Directorate-Africa 
P.O. Box 1357-20200 Kericho, Kenya. 
Phone: +25452-20-30686; Mobile: +254 708154971 Fax +254-52-20-30546 
Email: faith.riziki@usamru-k.org 
 
Ignatius Ngetich, BSc, MSc 
Data Manager 
Kenya Medical Research Institute/US Army Medical Research Directorate-Africa 
P.O. Box 1357-20200 Kericho, Kenya. 
Phone: +25452-20-30686; Mobile: +254 705251779 Fax +254-52-20-30546 
Email: ignatius.kiptoo@usamru-k.org 
 
Rael Bor, BSc 
RV460 Site Study Coordinator 
Kenya Medical Research Institute/US Army Medical Research Directorate-Africa 
P.O. Box 1357-20200 Kericho, Kenya. 
Phone: +25452-20-30686; Mobile: +254 729 110 121 Fax +254-52-20-30546 
Email: rael.bor@usamru-k.org 
 
LAB INVESTIGATOR LEAD 
Leigh Anne Eller, PhD 
U.S. Military HIV Research Program (MHRP)/ 
Walter Reed Army Institute of Research (WRAIR) 
6720A Rockledge Drive 
Bethesda, MD. USA 20817 
Phone: 301-500-3638 
Email : leller@hivresearch.org 
 
SITE LABORATORY INVESTIGATOR 
Ibrahim Daud, PhD 
Laboratory Director 
Kenya Medical Research Institute/US Army Medical Research Directorate-Africa 
P.O. Box 1357-20200 Kericho, Kenya. 
Phone: +25452-20-30686; Mobile: +254 726 487 199 Fax +254-52-20-30546 
Email: ibrahim.daud@usamru-k.org 


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SCIENTIFIC LEAD 
Gary Matyas, PhD 
U.S. Military HIV Research Program (MHRP)/ 
Walter Reed Army Institute of Research (WRAIR) 
503 Robert Grant Avenue 
Silver Spring, MD 20910 
Phone: 301-319-9973 
Email: gmatyas@hivresearch.org 
 
DAIDS MEDICAL OFFICER  
 
 
Laura Polakowski, MD, MSPH 
Medical Officer 
Vaccine Clinical Research Branch 
Vaccine Research Program 
Division of AIDS, NIAID, NIH 
5601 Fishers Lane, 9D11B 
Rockville, MD 20852 
Phone: 301-627-3040 
Email: laura.polakowski@nih.gov 
 
IND SPONSOR  
 
Division of AIDS  
National Institute of Allergy and Infectious Disease (NIAID) 
US National Institutes of Health 
 
DAIDS PROTOCOL PHARMACISTS 
 
Shawn Chiambah, PhD, RPh 
Pharmacist [C], Pharmaceutical Affairs Branch 
Division of AIDS/NIAID/NIH 
5601 Fishers Lane 
Room 9A26  MSC 9829 
Rockville, MD 20852 
Phone:  301-761-7336 
Email: shawn.chiambah@nih.gov 
 
PROTOCOL STATISTICIAN 
Chris Bryant  
Emmes 
401 North Washington Street 
Rockville, MD 20852  
Phone: 301-251-1161 
Email: cbryant@emmes.com 


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TABLE OF CONTENTS 
PROTOCOL TEAM ................................................................................................................................................... 2 
TABLE OF CONTENTS ............................................................................................................................................ 5 
LIST OF ABBREVIATIONS ................................................................................................................................... 11 
PROTOCOL SUMMARY ........................................................................................................................................ 18 
LAY SUMMARY ...................................................................................................................................................... 21 
ABSTRACT ............................................................................................................................................................... 22 
PRECIS ...................................................................................................................................................................... 23 
 
OBJECTIVES AND ENDPOINTS ................................................................................................................. 25 
 
OBJECTIVES ................................................................................................................................................... 25 
1.1.1 
Primary ................................................................................................................................................ 25 
1.1.2 
Secondary ............................................................................................................................................ 25 
1.1.3 
Exploratory .......................................................................................................................................... 25 
1.1.3.1 
Sub-objective .............................................................................................................................. 25 
 
ENDPOINTS ..................................................................................................................................................... 26 
1.2.1 
Primary ................................................................................................................................................ 26 
1.2.2 
Secondary ............................................................................................................................................ 26 
1.2.3 
Exploratory .......................................................................................................................................... 26 
1.2.4 
Sub-set of Participants that Elect to Undergo Lymph Node Biopsy .................................................... 27 
 
BACKGROUND AND SCIENTIFIC RATIONALE .................................................................................... 28 
 
BACKGROUND ................................................................................................................................................ 28 
2.1.1 
Purpose ................................................................................................................................................ 28 
 
SCIENTIFIC RATIONALE .................................................................................................................................. 31 
2.2.1 
Study Products and Dose Justification ................................................................................................. 31 
2.2.1.1 
Env-C Plasmid DNA (HIV-1 gp120 (93MW965.26) DNA) ...................................................... 31 
2.2.1.2 
HIV Env gp145 C.6980 Protein ................................................................................................. 31 
2.2.1.3 
ALF43: Army Liposome Formulation—43% Cholesterol ......................................................... 31 
2.2.1.4 
Recombinant Double Mutant Escherichia coli Heat Labile Toxin (dmLT) ............................... 31 
2.2.1.5 
Rehydragel® (Aluminum Hydroxide Fluid Gel) ....................................................................... 31 
2.2.2 
Overview of Pre-Clinical Study Results .............................................................................................. 31 
2.2.3 
Overview of Relevant Clinical Studies ................................................................................................ 33 
2.2.3.1 
Safety and Immunogenicity of the Env-C Plasmid DNA Alone or with an HIV Env Protein 
Boost Vaccine ............................................................................................................................................... 33 
2.2.3.2 
Safety and Immunogenicity of the HIV Env gp145 C.6980 protein (or other HIV-1 Env Protein 
Vaccines) Alone or with a Plasmid Vector expressing HIV-1 Env Antigens as a Prime Vaccination .......... 34 
2.2.3.3 
Safety and Immunogenicity Overview of Army Liposome Adjuvants ...................................... 35 
2.2.3.4 
Safety and Immunogenicity Overview of Rehydragel® ............................................................. 36 
2.2.3.5 
Safety and Immunogenicity Overview of Recombinant Double Mutant Escherichia coli Heat 
Labile Toxin (dmLT; R192G/L211A) ........................................................................................................... 37 
 
MILITARY RELEVANCE .................................................................................................................................. 38 
 
DESCRIPTION OF KERICHO SITE ..................................................................................................................... 39 
 
STUDY DESIGN ............................................................................................................................................... 40 
 
OBJECTIVES ................................................................................................................................................... 41 
2.6.1 
Primary ................................................................................................................................................ 41 
2.6.2 
Secondary ............................................................................................................................................ 41 


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2.6.3 
Exploratory .......................................................................................................................................... 42 
2.6.4 
Sub-objective ....................................................................................................................................... 42 
 
ENDPOINTS ..................................................................................................................................................... 42 
2.7.1 
Primary ................................................................................................................................................ 42 
2.7.2 
Secondary ............................................................................................................................................ 42 
2.7.3 
Exploratory .......................................................................................................................................... 43 
2.7.4 
Sub-set of Participants that Elect to Undergo Lymph Node Biopsy .................................................... 43 
 
INVESTIGATIONAL PRODUCTS ............................................................................................................... 44 
 
DESCRIPTION OF STUDY AGENTS ................................................................................................................... 44 
3.1.1 
Env-C Plasmid DNA Vaccine ............................................................................................................. 44 
3.1.2 
HIV-1 Env gp145 C.6980 .................................................................................................................... 44 
3.1.3 
Recombinant Double Mutant Escherichia coli Heat-Labile Toxin LT (R192G/L211A) (dmLT) ....... 44 
3.1.4 
ALF43: Army Liposome Formulation—43% Cholesterol .................................................................. 44 
3.1.5 
Aluminum Hydroxide Suspension—Fluid Gel (Rehydragel®) ............................................................ 44 
3.1.6 
0.9% Sodium Chloride for Injection (Sterile Saline) ........................................................................... 45 
 
ACQUISITION AND DISTRIBUTION .................................................................................................................. 46 
 
DOSAGE PREPARATION, DISPENSING AND ADMINISTRATION OF STUDY PRODUCT ........................................ 47 
3.3.1 
Preparation of Investigational Products ............................................................................................... 48 
3.3.1.1 
Env-C Plasmid DNA .................................................................................................................. 49 
3.3.1.2 
Placebo for Env-C Plasmid DNA ............................................................................................... 49 
3.3.1.3 
dmLT .......................................................................................................................................... 49 
3.3.1.4 
Placebo for dmLT....................................................................................................................... 50 
3.3.1.5 
Env-C Plasmid DNA + ALF43 .................................................................................................. 50 
3.3.1.6 
Placebo for Env-C Plasmid DNA + ALF43 ............................................................................... 51 
3.3.1.7 
Env-C Plasmid DNA + HIV Env gp145 C.6980 + ALF43 ........................................................ 51 
3.3.1.8 
Placebo for Env-C Plasmid DNA + HIV Env gp145 C.6980 Protein + ALF43 ........................ 52 
3.3.1.9 
HIV Env gp145 C.6980 Protein + Rehydragel® ......................................................................... 52 
3.3.1.10 
Placebo for HIV Env gp145 C.6980 Protein + Rehydragel® ...................................................... 53 
3.3.1.11 
HIV Env gp145 C.6980 Protein + ALF43 + Rehydragel® ......................................................... 53 
3.3.1.12 
Placebo for HIV Env gp145 C.6980 Protein + ALF43 + Rehydragel® ...................................... 54 
3.3.1.13 
Env-C Plasmid DNA + HIV Env gp145 C.6980 Protein + ALF43 + Rehydragel® ................... 54 
3.3.1.14 
Placebo for Env-C Plasmid DNA + HIV Env gp145 C.6980 Protein + ALF43 + Rehydragel® 55 
3.3.2 
Products Used for Dose Preparation and Administration .................................................................... 56 
3.3.2.1 
Sterile Water for Injection .......................................................................................................... 56 
3.3.2.2 
0.9% Sodium Chloride for Injection .......................................................................................... 56 
3.3.2.3 
Empty Sterile Vials .................................................................................................................... 56 
3.3.2.4 
ECG Skin Preparation Paper ...................................................................................................... 56 
3.3.2.5 
Sterile 2 x 2-inch, 12 Ply Gauze Pad .......................................................................................... 56 
3.3.2.6 
Nexcare™ Tegaderm™ Waterproof Transparent Dressing ....................................................... 56 
3.3.3 
Labelling to Preserve Blinding ............................................................................................................ 56 
3.3.4 
Experimental Vaccination Administration ........................................................................................... 57 
 
STUDY PRODUCT ACCOUNTABILITY .............................................................................................................. 57 
3.4.1 
Final Disposition of Study Products .................................................................................................... 58 
 
PARTICIPANT ELIGIBILITY AND MANAGEMENT ............................................................................. 59 
 
STUDY POPULATION ...................................................................................................................................... 59 
 
ELIGIBILITY CRITERIA.................................................................................................................................... 59 
4.2.1 
Inclusion Criteria ................................................................................................................................. 59 
4.2.2 
Exclusion Criteria ................................................................................................................................ 60 
 
LYMPH NODE BIOPSY ELIGIBILITY CRITERIA ................................................................................................ 61 
 
PARTICIPANT MANAGEMENT ......................................................................................................................... 62 


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4.4.1 
Participant responsibilities ................................................................................................................... 62 
4.4.2 
Withdrawal from the Study, Discontinuation of Study Product, or Study Termination ...................... 62 
4.4.2.1 
Withdrawal ................................................................................................................................. 62 
4.4.2.2 
Participant Replacement ............................................................................................................. 63 
4.4.2.3 
Early Discontinuation of Vaccinations or Withdrawal of a Study Participant ........................... 63 
4.4.3 
Management of Medical Conditions .................................................................................................... 63 
4.4.4 
Management of Participants Who Become Pregnant ........................................................................... 64 
4.4.5 
Management of Participants Who Become Incarcerated ..................................................................... 64 
4.4.6 
Management of Participants with Vaccine-Induced Seropositivity (VISP) or Seroreactivity (VISR). 64 
4.4.7 
Transportation ...................................................................................................................................... 64 
4.4.8 
Unblinding Procedures ........................................................................................................................ 65 
 
STUDY PROCEDURES .................................................................................................................................. 66 
 
RECRUITMENT ................................................................................................................................................ 66 
 
CONSENT PROCEDURES AND SCREENING ....................................................................................................... 66 
 
ENROLLMENT AND RANDOMIZATION ............................................................................................................. 67 
 
VACCINATION ................................................................................................................................................ 67 
 
STUDY VISITS ................................................................................................................................................ 68 
 
OPTIONAL PROCEDURES ................................................................................................................................. 70 
5.6.1 
Mucosal Collections ............................................................................................................................ 70 
5.6.1.1 
Female Participants .................................................................................................................... 70 
5.6.1.2 
Male Participants ........................................................................................................................ 71 
5.6.2 
Lymph Node Biopsies ......................................................................................................................... 71 
 
INFORMATION SHEET ON COVID-19 ............................................................................................................. 72 
 
LABORATORY ASSESSMENTS.................................................................................................................. 73 
 
BLOOD SAMPLES ............................................................................................................................................ 73 
6.1.1.1 
Laboratory tests to assess safety ................................................................................................. 73 
6.1.2 
Immunogenicity tests ........................................................................................................................... 73 
6.1.2.1 
HIV-1-specific binding antibody assays .................................................................................... 73 
6.1.2.2 
Functional antibody assays ......................................................................................................... 74 
6.1.2.3 
Neutralizing antibody assays ...................................................................................................... 74 
6.1.2.4 
Cellular immune assays .............................................................................................................. 74 
6.1.3 
Other assays ......................................................................................................................................... 74 
 
FUTURE USE AND STORAGE OF BIOLOGICAL SAMPLES .................................................................................. 74 
 
DATA MANAGEMENT AND ANALYSIS ................................................................................................... 76 
 
STUDY DOCUMENTATION, STORAGE, AND DATA COLLECTION ..................................................................... 76 
 
ANALYSIS ...................................................................................................................................................... 76 
7.2.1 
Power and Sample Size ........................................................................................................................ 76 
7.2.2 
Primary Analysis ................................................................................................................................. 78 
7.2.3 
Secondary Analysis ............................................................................................................................. 78 
7.2.4 
Exploratory and Subgroup Analyses ................................................................................................... 79 
 
SAFETY AND REPORTING ......................................................................................................................... 80 
 
ASSESSING AND RECORDING SAFETY PARAMETERS ...................................................................................... 80 
8.1.1 
Reactogenicity ..................................................................................................................................... 80 
8.1.1.1 
Diary Card (7-Day Solicited Reactogenicity) ............................................................................ 80 
8.1.2 
Management of Vaccination Reactions ............................................................................................... 81 
8.1.3 
Adverse Events (AEs) .......................................................................................................................... 81 
8.1.4 
Serious Adverse Events (SAEs) ........................................................................................................... 82 
8.1.5 
Potentially Immune-Mediated Medical Conditions (PIMMCs) ........................................................... 83 


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8.1.6 
Medically Attended Adverse Events ................................................................................................... 83 
8.1.7 
Adverse Event Assessment .................................................................................................................. 83 
8.1.8 
Adverse Event Documentation ............................................................................................................ 84 
8.1.8.1 
Severity vs. Seriousness of Adverse Events ............................................................................... 84 
8.1.8.2 
Relationship to Study Product .................................................................................................... 84 
8.1.8.3 
Expectedness .............................................................................................................................. 85 
8.1.8.4 
Type and Duration of Follow-up of Participants after Adverse Events...................................... 85 
 
EXPEDITED ADVERSE EVENT (EAE) REPORTING ........................................................................................... 85 
8.2.1 
EAE Reporting ..................................................................................................................................... 85 
8.2.1.1 
EAE Reporting Requirements for the Study .............................................................................. 86 
8.2.1.2 
Grading Severity of EAEs .......................................................................................................... 86 
8.2.1.3 
EAE Reporting Period ................................................................................................................ 86 
8.2.1.4 
Submission of Updated Information on Expedited Adverse Events .......................................... 87 
8.2.1.5 
Reporting Recurrent Adverse Events on an Expedited Basis ..................................................... 87 
 
HALTING OR PAUSING RULES ........................................................................................................................ 87 
8.3.1 
Notification of AEs Meeting Study Pause Criteria .............................................................................. 87 
8.3.2 
Plan for Review of Pauses and Resuming Rules ................................................................................. 88 
 
SAFETY OVERSIGHT ....................................................................................................................................... 88 
8.4.1 
Safety Monitoring Committee (SMC) ................................................................................................. 88 
8.4.2 
Department of Defense (DoD) Research Monitor ............................................................................... 89 
 
HUMAN SUBJECTS PROTECTION ........................................................................................................... 90 
 
INFORMED CONSENT ...................................................................................................................................... 90 
 
POTENTIAL RISKS AND BENEFITS ................................................................................................................... 91 
9.2.1 
Potential Risks ..................................................................................................................................... 91 
9.2.1.1 
Risks of Study Agent Administration and Their Mitigation ...................................................... 91 
9.2.1.2 
Vaccine-Induced Seropositivity (VISP) or Seroreactivity (VISR) ............................................. 92 
9.2.1.3 
Social Harms .............................................................................................................................. 93 
9.2.1.4 
Unknown Risks .......................................................................................................................... 93 
9.2.1.5 
Unknown Risks related to Immune-Based Diseases .................................................................. 93 
9.2.1.6 
Study Risks Related to Pregnancy and Their Mitigation ............................................................ 93 
9.2.1.7 
Risks of Phlebotomy .................................................................................................................. 94 
9.2.1.8 
Risks Related to Mucosal Secretion Collection ......................................................................... 94 
9.2.1.9 
Risks Related to Lymph Node Biopsy ....................................................................................... 94 
9.2.1.10 
Risks from Human Leukocyte (HLA) testing ............................................................................ 94 
9.2.1.11 
Risks to Researchers ................................................................................................................... 95 
9.2.2 
Potential Benefits ................................................................................................................................. 95 
 
COMMUNITY ADVISORY BOARD (CAB) ........................................................................................................ 95 
 
MANAGEMENT OF VULNERABLE POPULATIONS ............................................................................................. 95 
9.4.1 
Participation of Children ...................................................................................................................... 96 
9.4.2 
Participation of Prisoners ..................................................................................................................... 96 
9.4.3 
Illiterate Participants ............................................................................................................................ 96 
 
FUTURE USE AND STORAGE OF BIOLOGICAL SAMPLES .................................................................................. 96 
 
RISKS FROM HUMAN LEUKOCYTE (HLA) AND OTHER GENETIC TESTING ..................................................... 97 
 
PARTICIPANT CONFIDENTIALITY .................................................................................................................... 97 
 
COSTS, REIMBURSEMENT, AND RESEARCH RELATED INJURIES ...................................................................... 97 
9.8.1 
Policy Regarding Research-Related Injuries ....................................................................................... 97 
9.8.2 
Reimbursement .................................................................................................................................... 97 
 
INSTITUTIONAL REVIEW BOARDS AND REGULATORY REQUIREMENTS ................................ 99 
 
INSTITUTIONAL REVIEW BOARDS .............................................................................................................. 99 
10.1.1 
Reporting Requirements to the KEMRI SERU ............................................................................... 99 


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10.1.2 
Additional Local Regulatory Authority .......................................................................................... 99 
 
REGULATORY REPORTING ....................................................................................................................... 100 
10.2.1 
Immediate and Continuing Review Reporting to the DoD ........................................................... 100 
10.2.2 
Reporting and Management of Participants Who Become Pregnant ............................................ 100 
10.2.3 
Reporting and Management of Participants Who Become Incarcerated ....................................... 101 
10.2.4 
Social Harms Reporting ................................................................................................................ 101 
 
PROTOCOL DEVIATIONS .......................................................................................................................... 101 
10.3.1 
Major ............................................................................................................................................. 102 
10.3.2 
Minor ............................................................................................................................................ 102 
 
PROTOCOL AMENDMENTS ....................................................................................................................... 103 
 
CONTINUING REVIEWS AND CLOSEOUT REPORTS ................................................................................... 103 
 
REGULATORY AUDITS ............................................................................................................................. 103 
 
ESSENTIAL AND SOURCE DOCUMENTS ............................................................................................. 104 
 
SOURCE DOCUMENTS .............................................................................................................................. 104 
 
ESSENTIAL DOCUMENTS ......................................................................................................................... 104 
 
ADMINISTRATIVE AND LEGAL OBLIGATIONS ................................................................................ 105 
 
CONDUCT OF THE RESEARCH STUDY ...................................................................................................... 105 
 
PROTOCOL REGISTRATION ...................................................................................................................... 105 
12.2.1 
Initial Registration......................................................................................................................... 105 
12.2.2 
Amendments ................................................................................................................................. 105 
 
COMPLIANCE WITH NIH GUIDELINES FOR RESEARCH INVOLVING PRODUCTS CONTAINING RECOMBINANT 
DNA 
105 
 
SPONSOR STUDY MONITORING ............................................................................................................... 106 
 
BIOHAZARD CONTAINMENT .................................................................................................................... 106 
 
EXPECTED APPLICATION OF RESULTS ..................................................................................................... 106 
 
USE OF INFORMATION AND PUBLICATION ............................................................................................... 107 
 
VOLUNTEER REGISTRY DATA SHEET ...................................................................................................... 107 
 
PRINCIPAL INVESTIGATOR AGREEMENT......................................................................................... 108 
 
LITERATURE REFERENCES.................................................................................................................... 110 
 
KERICHO BUDGET AND TIMEFRAME ................................................................................................. 118 
 
KERICHO BUDGET ................................................................................................................................... 118 
15.1.1 
Kericho Budget Justification ......................................................................................................... 118 
15.1.1.1 
Personnel .................................................................................................................................. 118 
15.1.1.2 
Equipment ................................................................................................................................ 118 
15.1.1.3 
Supplies .................................................................................................................................... 118 
15.1.1.4 
Travel ....................................................................................................................................... 118 
15.1.1.5 
Other expenses ......................................................................................................................... 119 
15.1.1.6 
Overheads ................................................................................................................................. 119 
 
TIME FRAME AND DURATION AT KERICHO ............................................................................................. 120 
 
APPENDICES ................................................................................................................................................ 121 
 
SCHEDULE OF EVALUATIONS ............................................................................................... 122 
 
MAIN INFORMED CONSENT FORM ........................................................................................ 125 
 
OPTIONAL PROCEDURES CONSENT ....................................................................................... 143 
 
PHOTOGRAPHY CONSENT FORM  .......................................................................................... 153 
 
WITHDRAWAL OF CONSENT FORM ....................................................................................... 156 
 
TEST OF UNDERSTANDING ................................................................................................... 159 
 
PARTICIPANT VISIT SCHEDULE ............................................................................................ 162 


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RISK ASSESSMENT TOOL ...................................................................................................... 167 
 
DIARY CARD ............................................................................................................................. 169 
 
EMERGENCY CONTACT CARD .............................................................................................. 172 
 
VISP LETTER ....................................................................................................................... 174 
 
UNBLINDING LETTER ........................................................................................................... 176 
 
ROLES AND RESPONSIBILITIES ............................................................................................. 180 
 
PARTICIPATING LABORATORIES ........................................................................................... 183 
 
LIST OF PIMMCS ................................................................................................................. 186 
 
EXTERNAL COLLABORATORS ............................................................................................... 190 
 
TELEPHONE VISIT SCRIPT ..................................................................................................... 192 
 
BRIEFING SLIDES .................................................................................................................. 194 
ATTACHMENT 1: COVID INFORMATION SHEET ....................................................................................... 202 
 
LIST OF TABLES 
Table 1: Study Design ................................................................................................................................................. 40 
Table 2: Study Agents ................................................................................................................................................. 45 
Table 3: Study Groups ................................................................................................................................................. 48 
Table 4: Visit Procedures............................................................................................................................................. 69 
Table 5: Estimated probability (in percent) of a participant having at least one AE, along with the 
associated exact Clopper-Pearson 95% CI, given varying sample sizes and numbers of 
participants with at least one observed AE ........................................................................................... 77 
Table 6: Probability of observing at least one or at least two safety events in a given group, given varying 
underlying per-participant probabilities of experiencing at least one event.......................................... 78 
Table 7: Time Frame and Duration at Kericho .......................................................................................................... 120 
  
 
 


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LIST OF ABBREVIATIONS 
AABB 
American Association of Blood Banks 
Ab  
Antibodies 
ACTG 
Aids Clinical Trials Group 
ADC 
Antibody-Dependent Complement 
ADCC 
Antibody-Dependent Cell-Mediated Cytotoxicity 
ADCP 
Antibody-Dependent Cell-Mediated Phagocytosis 
ADCVI 
Assay and Antibody-Dependent Cell Mediated Viral Inhibition 
AE 
Adverse Event 
AESI 
Adverse Events of Special Interest 
AFRIMS 
Armed Forces Research Institute of Medical Sciences 
AIDS 
Acquired Immune Deficiency Syndrome 
AIDSVAX 
HIV gp120 in Aluminum Hydroxide (Rehydragel®) 
ALF 
Army Liposome Formulation 
ALF43 
ALF43 Army Liposome Formulation with Monophosphoryl 
Lipid A (MPLA) and 43% Cholesterol 
ALF43A 
ALF43 Combined with Aluminum Salt-Based Adjuvant Such as 
Rehydragel® or Alhydrogel® 
AlOH 
Aluminum Hydroxide 
ALT 
Alanine Aminotransferase 
Alum 
Aluminum Salt 
ALVAC 
HIV Antigen-Expressing Viral Vector - Canarypox Vector 
APGAR 
American Pediatric Gross Assessment Record 
AST 
Aspartate Aminotransferase 
AVEG 
AIDS Vaccine Evaluation Group 
BP 
Blood Pressure 
BB-IND 
Biologics Investigational New Drug Application 
BB-MF 
Biologics Master File 
BMI 
Body Mass Index 
bNAbs 
Broadly Neutralizing Antibodies 


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CA  
Cooperative Agreement 
CAB 
Community Advisory Board 
CAP 
College of American Pathologists 
CBC 
Complete Blood Count 
CCR7 
C-C Chemokine Receptor Type 7  
CD4 
Cluster of Differentiation 
CDMRP   
Congressionally Directed Medical Research Programs 
CfaE 
ETEC Adhesion Antigen 
CFR 
Code of Federal Regulation 
CK 
Creatine Kinase 
COO 
Clinical Operations Office, MHRP 
CRC 
Clinical Research Center, KEMRI, USAMRD-A 
CRFs 
Case Report Forms 
CRFs 
HIV Circulating Recombinant Forms 
CROMC 
Clinical Research Products Management Center, NIAID 
CXCR5 
C-X-C Chemokine Receptor Type 5 
DAERS 
DAIDS Adverse Experience Reporting System 
DAIDS 
Division of AIDS 
DCAC 
Data Coordinating and Analysis Center, MHRP 
dmLT 
Double Mutant Heat-Labile Enterotoxin 
DMPC 
Dimyristoylphosphatidylcholine 
DMPG 
Dimyristoylphosphatidylglycerol 
DNA                              
Deoxyribonucleic Acid 
DoD 
Department of Defense 
dscCfaE 
Donor Strand Complemented Cfae (Recombinant E. coli 
Protein) 
DTH 
Delayed-Type Hypersensitivity 
EAE 
Expedited Adverse Events 
EC 
Ethics Committee 
ECCT 
Kenya Expert Committee on Clinical Trials, PPB 


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ELISPOT 
Enzyme-Linked Immunospot  
EMA 
European Medicines Agency 
ENV-C Plasmid DNA 
HIV-1 gp120 (93MW965.26) DNA 
Env 
Envelope 
ETEC 
Enterotoxigenic E. coli 
FDA 
Food and Drug Administration 
FDR 
False Discovery Rate 
FSH 
Follicle-stimulating Hormone 
GCLP 
Good Clinical Laboratory Practices 
GCP 
Good Clinical Practices 
GI 
Gastrointestinal 
HIV Env gp145 C.6980 
gp145 C.6980 Clade C HIV-1 Env Protein 
GSK 
GlaxoSmithKline 
GU 
Genitourinary 
H20 
Water 
HBsAg 
Hepatitis B Surface Antigen 
HIV-1 
Human Immunodeficiency Virus 1 
HJF 
Henry M. Jackson Foundation for the Advancement of Military 
Medicine 
HLA 
Human Leukocyte Antigen 
HRPO 
Human Research Protections Office 
HSP 
Henoch-Schönlein Purpura 
HSPB 
Human Subject Protection Branch 
HVTN 
HIV Vaccine Trials Network 
IB                                    
Investigator’s Brochure 
IBC 
Institutional Biosafety Committee 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
ICOS 
Inducible T Cell Co-Stimulator 
ICS 
Intra-Cellular Cytokine Staining 
ID 
Intradermal 


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IFN  
Interferon 
IFN-γ  
Interferon-Gamma 
Ig 
Immunoglobulin 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IL 
Interleukin 
IL-21 
Interleukin-21 
IM 
Intramuscular 
IMPAACT 
International Maternal Pediatric Adolescent AIDS Clinical Trials 
IND 
Investigational New Drug Application 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IT 
Information Technology 
IUD 
Intrauterine Device 
IV 
Intravenous 
KCRH 
Kericho County Referral Hospital 
KEMRI 
Kenya Medical Research Institute 
KSH 
Kenyan Shillings 
LH 
Luteinizing Hormone 
L(MPLA) 
Liposome Containing Monophosphoryl Lipid A 
LN 
Lymph Nodes 
LPA 
Lymphoproliferation Assays 
LT 
Heat-Labile Enterotoxin (E. coli) 
mAb 
Monoclonal Antibody 
MD  
Maryland 
MF 
Master File 
MHRP 
US Military HIV Research Program 
mL  
Milliliter 
mLT 
Mutant LT 


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MO 
Medical Officer, DAIDS 
MoH 
Kenya Ministry of Health 
MPLA 
Monophosphoryl Lipid A 
MPL® 
Monophosphoryl Lipid A (Owned by GSK) 
USAMRD-A 
United States Army Medical Research Directorate-Africa  
MS 
Multiple Sclerosis 
MVA 
Modified Vaccinia Ankara 
NaCl 
Sodium Chloride 
NCT 
National Clinical Trial                
NHP 
Nonhuman Primate 
NIAID 
The National Institute of Allergy and Infectious Diseases 
NIH 
National Institutes of Health 
NK 
Natural Killer Cell 
NSAIDS 
Non-Steroidal Anti-Inflammatory Drugs 
OBA 
Office of Biotechnology Activities, NIH 
ORP 
Office of Research Protection 
ORTA 
Office of Research Technology and Applications 
PBMC 
Peripheral Blood Mononuclear Cell 
PD-1 
Programmed Cell Death Protein-1 
PEP 
Post-Exposure Prophylaxis 
PI 
Principal Investigator 
PID 
Participant Identification 
PIR 
Post-Injection Reactogenicity 
PPB 
Pharmacy and Poisons Board 
PPE 
Personal Protective Equipment 
PSRT 
Protocol Safety Review Team 
QS-21 
Quillaja Saponaria 21 (Fraction 21 of Purified Extract) 
R4P 
HIV Research for Prevention 
RAC 
Recombinant DNA Advisory Committee 


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RR 
Respiratory Rate 
RSC 
Regulatory Support Center, DAIDS 
RT 
Room Temperature 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SERU 
Scientific and Ethics Review Unit, KEMRI 
SIV 
Simian Immunodeficiency Virus 
SMC 
Safety Monitoring Committee, MHRP 
SOE 
Schedule of Evaluations 
SOP 
Standard Operating Procedure 
STI 
Sexually Transmitted Infections 
SUSAR  
Serious, Unexpected, Suspected Adverse Drug Reaction 
TB 
Tuberculosis 
TCI 
Transcutaneous Immunization 
TEMP 
Temperature 
Tfh 
T Follicular Helper Cell 
Tfr 
T Follicular Regulatory 
TNF-α 
Tumor Necrosis Factor 
TOU 
Test of Understanding 
UNAIDS 
Joint United Nations Programme on HIV/AIDS 
UPIRTSO 
Unanticipated Problems Involving Risk to Participants or Others 
USAMMDA 
United States Army Medical Material Development Activity 
USAMRAA 
United States Army Medical Research Acquisition Activity 
USAMRDC 
U.S. Army Medical Research and Development Command  
USD 
U.S. Dollars 
VISP 
Vaccine-Induced Seropositivity 
VISR 
Vaccine-Induced Seroreactivity 
WB 
Whole Blood 
WHO 
World Health Organization 


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WRAIR 
Walter Reed Army Institute of Research 
 
 
 
 


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PROTOCOL SUMMARY 
Title: 
A Randomized, Double-Blind Phase 1 Trial to Evaluate the Safety and 
Immunogenicity of Priming with Env-C Plasmid DNA Vaccine Alone, 
with Different Adjuvants, or with an Adjuvanted HIV Env gp145 C.6980 
Protein Vaccine and Boosting with the Adjuvanted HIV Env gp145 C.6980 
Protein Vaccine with or without the Env-C Plasmid DNA Vaccine in 
Healthy HIV Uninfected Adults in Kenya 
Design: 
 
RV460 is an exploratory study that will assess the safety, tolerability, and 
immunogenicity of a vaccine regimen consisting of priming with an Env-
C Plasmid DNA vaccine (with or without novel adjuvants) when given 
with or without adjuvanted HIV Env gp145 C.6980 protein vaccine and 
boosting with adjuvanted gp145 C.6980 protein with or without the gp120 
DNA vaccine.  The study will be carried out at the KEMRI/US Army 
Medical Research Directorate-Africa (USAMRD-A), Clinical Research 
Centre, Kericho; and 126 healthy adults will be enrolled.  Participants 
enroll randomly into one of seven groups which have 15/3 vaccine/placebo 
recipients per group. Each participant will receive six injections (prime at 
week 0, 4, 12; boost at week 20, 32 and 56) followed up for a total of 108 
weeks.  
Study objectives will be met by the testing of blood samples from all 
participants.  Willing and eligible participants have the option to provide 
lymph node and mucosal secretion samples (semen, cervicovaginal, 
rectal), which will provide the data for objectives 2 and the sub-objectives.  
Phase: 
1 
Population: 
126 Healthy, HIV-uninfected male and female participants aged 18 to 40 
years in Kericho, Kenya 
Number of Sites: 
1  
Products: 
• Env-C Plasmid DNA (HIV-1gp120 (93MW965.26) DNA)  
• HIV Env gp145 C.6980 protein 
• Double Mutant of Heat Labile E. coli enterotoxin (dmLT) 
• ALF43: Army Liposome Formulation—43% Cholesterol*  
• Aluminum Hydroxide Suspension—Fluid Gel (Rehydragel®) * 


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*From this point forward, Army Liposome Formulation—43% 
Cholesterol will be referred to as ALF43 and Aluminum Hydroxide 
Suspension—Fluid Gel will be referred to as Rehydragel® 
Objectives: 
 
Primary 
Exploratory study to assess the safety and tolerability (including 
reactogenicity) of Env-C Plasmid DNA given IM alone, admixed with 
ALF43 adjuvant, topically applied with dmLT adjuvant, or given with an 
adjuvanted HIV Env gp145 C.6980 protein and followed by adjuvanted 
HIV Env gp145 C.6980 boost IM vaccinations, with or without Env-C 
Plasmid DNA. 
Secondary 
Assess the immunogenicity of the various study vaccine combinations: 
1. Determine whether the adjuvants under study 
improve the immunogenicity of the Env-C Plasmid 
DNA priming.  
2. Determine whether the addition of ALF43 to the 
Rehydragel® –HIV Env gp145 C.6980 protein boost 
further improves the immune response to HIV Env 
gp145 C.6980 protein. 
3. Determine whether adjuvants improve humoral 
responses across vaccination regimens.  
4. To evaluate the influence of various adjuvants on 
cellular immune responses.  
5. Describe mucosal humoral responses across 
vaccination regimens in cervicovaginal and rectal 
secretions and semen. 
Exploratory 
1. Characterize B-cell functional specificities for each 
vaccination regimen. 
2. Characterization of innate immunity. 
3. Assess the innate/gene expression induced across 
vaccination regimens (DNA microarray, RNA 
sequencing) to compare relative influence of various 


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adjuvants in the gene expression profiles sorted T 
cell, B cell, and innate cell subsets. 
4. Perform systems serology analyses.  
Sub-objective 
In participants who elect to undergo lymph node biopsy, characterize HIV-
specific responses, T cell activation, T follicular helper (Tfh) cell and B 
cell distribution in intact lymph nodes (excision of intact peripheral 
inguinal lymph node) at weeks 14 and 58. 
 
Duration of 
Individual Subject 
Participation 
Each participant will be enrolled for 108 weeks (105 weeks of clinic visits 
and then contact by phone once weekly for an additional three weeks to 
inquire about medically attended adverse events).   
 
Estimated Time to 
Last Subject/Last 
Visit 
Approximately 137 weeks (about 2 years, 8 months) 
 
 
 
 


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LAY SUMMARY 
The Kenya Medical Research Institute (KEMRI) in collaboration with the U.S. Military HIV 
Research Program (MHRP) is conducting a study on HIV vaccines.  A vaccine is a medical product 
given to prevent certain diseases, most often infectious diseases.  The vaccine may educate the 
human body to form a defensive response to try to prevent the disease from the beginning or taking 
hold of the body.  This defensive response called the immune response, and it is the body’s way 
to fight infections.  
The experimental HIV vaccines tested in this study are Env-C Plasmid DNA and HIV Env gp145 
C.6980 protein given with different adjuvants to increase the immune response.  An adjuvant is a 
substance added to vaccines that can help to make the vaccine more effective by improving the 
immune response or causing the immune response to last longer than without the adjuvant.  These 
adjuvants are mixed with the vaccines and injected into the muscle or placed on top of the skin.  
The HIV vaccines contain a piece of genetic material or a protein copied from the HIV virus cover 
(Env), but they do not contain the virus itself.  The vaccines cannot cause HIV infection or 
Acquired Immune Deficiency Syndrome (AIDS).  
The purpose of this study is to find out if the study vaccines with adjuvants cause side effects and 
are tolerable, whether humans respond, (develop immune responses) to the vaccines, and how long 
the effects of study vaccines last.  This study will also compare the effects (both good and bad) of 
the study vaccines with adjuvants and adjuvant patch to those of placebo injections and placebo 
patch.  The placebo will consist of saline (sterile saltwater), look just like the study vaccines with 
adjuvants and will be given the same way, but will have no active vaccine or adjuvant in it.  
Study objectives will be met by the testing of blood samples from all participants.  Willing and 
eligible participants have the option to provide lymph node and mucosal secretion samples (semen, 
cervicovaginal, rectal) will provide the data for objectives 2 and the sub-objections. 
The sponsor of this study is National Institute of Allergy and Infectious Diseases (NIAID) Division 
of AIDS (DAIDS), and the Military HIV Research Program (MHRP), a part of the Walter Reed 
Army Institute of Research (WRAIR), funds it.  A total of 126 participants will take part in this 
study.  
 


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ABSTRACT 
A safe and effective HIV vaccine would be the cornerstone for cost-effective, user-independent 
prevention methods against HIV infection.  Most of the successfully licensed vaccines for 
prevention of infections have historically relied upon aluminum salt (alum) formulations as 
adjuvants because they generally improve protective antibody magnitudes over the vaccine antigen 
alone and are reliably safe.   
Antibodies are the most commonly recognized correlate of vaccine protection from infection; 
however, the possible protective HIV antibody levels, which were induced by the modestly 
protective RV144 vaccine regimen with alum, rapidly decayed.  Potentially, a novel, highly 
selective adjuvant combined with the correctly sequenced HIV antigen could slow antibody decay, 
increase antibody magnitude, and induce antibodies of appropriate functional response.  
RV460 is an exploratory study that will assess the safety, tolerability, and immunogenicity of a 
vaccine regimen consisting of priming with an Env-C Plasmid DNA vaccine (with or without 
novel adjuvants) when given with or without adjuvanted HIV Env gp145 C.6980 protein vaccine 
and boosting with adjuvanted gp145 C.6980 protein with or without the gp120 DNA vaccine.  The 
study will be carried out at the KEMRI/US Army Medical Research Directorate-Africa 
(USAMRD-A), Clinical Research Centre, Kericho; and 126 healthy adults will be enrolled.  
Participants enroll randomly into one of seven groups which have 15/3 vaccine/placebo recipients 
per group.  Each participant will receive six injections (prime at week 0, 4, 12; boost at week 20, 
32 and 56) followed up for a total of 108 weeks.   
Study objectives will be met by the testing of blood samples from all participants.  Willing and 
eligible participants have the option to provide lymph node and mucosal secretion samples (semen, 
cervicovaginal, rectal), which will provide the data for objectives 2 and the sub-objections.  
Exploratory objectives may be met by genetic analysis including but not limited to Human 
Leukocyte Antigen (HLA) subtyping. 


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PRECIS  
Title  
A Randomized, Double-Blind Phase 1 Trial to Evaluate the Safety and Immunogenicity of Priming 
with Env-C Plasmid DNA Vaccine Alone, with Different Adjuvants, or with an Adjuvanted HIV 
Env gp145 C.6980 Protein Vaccine and Boosting with the Adjuvanted HIV Env gp145 C.6980 
Protein Vaccine with or without the Env-C Plasmid DNA Vaccine in Healthy HIV Uninfected 
Adults in Kenya 
Clinical Phase 
Phase 1 
Study Duration 
Participants are seen in the clinic for 105 weeks following enrollment and randomization.  
Participants will be contacted by phone once weekly for an additional three weeks to inquire about 
medically attended adverse events.  The total study-related activities may last up to 6 years (2-3 
years screening and clinical activities; 2-3 years of laboratory assays and data analyses). 
Participants 
Healthy, HIV-uninfected male and female volunteers aged 18 to 40 years.  
There will be 18 participants per group (15 vaccine recipients and 3 placebo recipients).  
Investigators will be blinded to vaccine versus placebo within each group but not across groups.  
Participants will be block randomized.   Group 1 (with a prime of Env-C Plasmid DNA IM alone 
at weeks 0, 4, 12) will be fully enrolled first.  After the 18 participants in Group 1  are enrolled, 
the remaining groups, 2-7, will begin enrolling participants.  Once 24 participants in Groups 2-7 
have been enrolled (four from each group) and received their first vaccinations, enrollment and 
vaccinations in Groups 2-7 will be paused for the time it takes the PSRT to review (typically 3 to 
14 days) blinded safety data from these 24 participants covering the period immediately after their 
first vaccination through Day 7.  If it is determined to be necessary by the PSRT, the MHRP SMC 
will be consulted to review unblinded data to provide a recommendation on continuing enrollment. 
When safety has been confirmed with PSRT review, the remaining 14 participants in each of 
Groups 2-7 will be enrolled, and vaccinations will continue until the first 24 participants in Groups 
2-7 (four per group) have received their first boost dose (at 20 weeks—to create a time gap between 
boost vaccinations of the first cohort and the remaining study participants).   
A second scheduled pause  (this pauses boost vaccinations only; prime vaccinations can continue) 
will occur for Groups 2-7 after the same set of participants reviewed during the first scheduled 
pause (the first 24 participants (four per group) from Groups 2-7) has received its first boost (Group 
1 can continue receiving vaccinations).  This pause will review blinded safety data from these 24 
participants, covering the period from the first boost through Day 7 after that boost.  At both 
scheduled pauses, the PSRT will consult the SMC regarding the pause if either of the following 
conditions are met: 1) one (or more) participants experience an SAE that is related to a study agent, 
or 2) two (or more) participants experience grade 3 or 4 AEs of the same type (e.g. elevated ALT) 


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related to a study agent.  Boost vaccinations for Groups 2-7 will resume once safety data from the 
booster sentinel cohort have been reviewed by the PSRT and they have concluded it is safe to 
proceed. 
Specific details of the randomization will be described in a separate randomization plan.   


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 OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
1.1.1 PRIMARY 
Exploratory study to assess the safety and tolerability (including reactogenicity) of HIV 
Env-C Plasmid DNA given IM alone, admixed with ALF43 adjuvant, topically applied 
with dmLT adjuvant, or given with an adjuvanted HIV Env gp145 C.6980 protein and 
followed by adjuvanted HIV Env gp145 C.6980 protein boost IM vaccinations, with or 
without Env-C Plasmid DNA. 
1.1.2 SECONDARY 
1. Assess the immunogenicity of the various study vaccine combinations: 
Determine whether the adjuvants under study improve the immunogenicity of 
the HIV Env-C Plasmid DNA priming.  
2. Determine whether the addition of ALF43 to the Rehydragel® /HIV Env gp145 
C.6980 protein boost further improves the immune response to HIV Env gp145 
C.6980 protein. 
3. Determine whether adjuvants improve humoral responses across vaccination 
regimens.  
4. To evaluate the influence of various adjuvants on cellular immune responses.  
5. Describe mucosal humoral responses across vaccination regimens in 
cervicovaginal and rectal secretions and semen. 
1.1.3 EXPLORATORY 
1. Characterize B-cell functional specificities for each vaccination regimen. 
2. Characterization of innate immunity. 
3. Assess the innate/gene expression induced across vaccination regimens (DNA 
microarray, RNA sequencing) to compare relative influence of various 
adjuvants in the gene expression profiles sorted T cell, B cell and innate cell 
subsets. 
4. Perform systems serology analyses.  
Exploratory objectives may be met by genetic analysis including but not limited to Human 
Leukocyte Antigen (HLA) subtyping. 
1.1.3.1 
Sub-objective   
In participants who elect to undergo lymph node biopsy, characterize HIV-specific 
responses, T cell activation, T follicular helper (Tfh) cell and B cell distribution in intact 
lymph nodes (excision of intact peripheral inguinal lymph node) at weeks 14 and 58. 


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ENDPOINTS 
1.2.1 PRIMARY   
Safety endpoints will be the solicited AE (local and systemic reactogenicity), and related AEs and 
SAEs. 
1.2.2 SECONDARY 
1. Comparison of plasma IgG binding antibodies to gp120 and V1V2 in terms of 
magnitude, durability, and area under the curve both after initial Env-C Plasmid 
DNA priming series among groups with differing Env-C Plasmid DNA priming 
regimens. 
2. Comparison of plasma IgG binding antibodies to gp120 and V1V2 in terms of 
magnitude, durability, and area under the curve between groups with and 
without Rehydragel® after HIV Env gp145 C.6980 protein boosting. 
3. Characterize plasma IgG and IgA binding antibodies to HIV gp120, V1V2, 
neutralizing antibodies, and non-neutralizing effector functions such as ADCC 
and ADCP with emphasis on RV144 immune correlates of risk of HIV 
acquisition. 
4. Characterize and assess the magnitude of cell-mediated immune responses 
elicited across vaccination regimens including but not limited to antigen -
specific CD4 and CD8 T cell responses and polyfunctionality, induced 
cytokines, chemokines and other inflammatory markers. 
5. Characterize mucosal humoral responses in cervicovaginal and rectal secretions 
and semen including, but not limited to, plasma IgG and IgA binding antibodies 
to HIV Env proteins, IgG and IgA subclass, and functional assays. 
1.2.3 EXPLORATORY 
1. Characterize B-cell functional specificities for each vaccination regimen by 
quantifying antigen-specific responses through B-cell ELISPOT, phenotyping 
the magnitude and activation status of B cell subsets via flow cytometry and 
isolation of monoclonal antibodies from selected vaccine recipients. 
2. Characterize innate immunity through quantification of soluble chemokines and 
cytokines and assessing the phenotype and function of cellular innate immune 
subsets such as NK, NKT, and dendritic cells. 
3. Compare relative influence of various adjuvants in the gene expression profiles 
sorted T cell, B cell and innate cell subsets using RNAseq and related methods 
to quantify and compare gene expression from various sorted cell subsets 
among study groups. 
4. Utilizing 
systems 
serology 
analyses, 
link 
various 
immunological 
measurements, including antibody-binding data to antibody effector functional 


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assays to evaluate immunologic response patterns or signatures to various 
adjuvants. 
1.2.4 SUB-SET OF PARTICIPANTS THAT ELECT TO UNDERGO LYMPH NODE BIOPSY   
Between each adjuvant group, compare the magnitude and frequency of HIV-specific TfH 
cells in total lymph nodes and lymph node follicles, TfH and B cell distribution between 
intra and extrafollicular LN zones, and levels of cellular activation using ICS, 
immunohistochemistry, transcriptional analyses, and related techniques at weeks 14 and 
58.  


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 BACKGROUND AND SCIENTIFIC RATIONALE 
 
BACKGROUND  
2.1.1 PURPOSE 
In the RV144 trial, a canarypox viral vector without an adjuvant and gp120 in combination with 
the conventional adjuvant, aluminum hydroxide was tested.  The proposed clinical trial, RV460, 
will explore the immune responses of adjuvanted Env-C Plasmid DNA in the context of the 
prime/boost vaccine platform.  RV460 represents an innovative strategy, guided by the results of 
RV144, to ascertain the ability of Env-C Plasmid DNA and HIV Env gp145 C.6980 protein 
antigens tested in combination with various adjuvants in prime and boost combinations given Env-
C Plasmid DNA in conjunction with adjuvants to induce potent and durable adaptive immunity 
against HIV-1 with emphasis on antibodies to the V1V2 protein loop.  
DNA is easily manufactured at low cost and has an increased stability profile compared to 
recombinant proteins [1], [2], [3, 4].  Thus, it is the ideal candidate for use as a vaccine.  In general, 
DNA vaccines are highly effective in small animal models, including mice and rabbits, but are 
poorly immunogenic in humans [3], [5].  Therefore, different immunization and formulation 
approaches have been explored to increase the immunogenicity of the DNA.  One strategy has 
been to immunize with DNA as an immune system priming immunization followed by a boost 
immunization with protein.  This method has been effective, but is cumbersome, requiring multiple 
immunizations and vaccine components.  In addition, a safe, effective adjuvant may also achieve 
a “dose-sparing” effect, i.e., the adjuvant may result in a reduction in the vaccine component 
dosage needed to elicit the desired immune response. Following immunization, the DNA is 
transcribed and translated into the protein antigen for uptake by antigen presenting cells for 
induction of antigen-specific immune responses.  In the presence of adjuvants, this process may 
become more efficient, since one of the roles of the adjuvant is to activate and recruit antigen 
presenting cells into the injection site.  These antigen-presenting cells take up antigen and migrate 
to the lymph nodes.  There they will present the antigen to T follicular helper (Tfh) cells that 
provide help to both B and T cells to induce high antibody titers and potent cellular immunity. 
Most of the animal and human studies with DNA vaccines have centered on the use of molecular 
adjuvants, such as CpG or cytokines, delivered as DNA together with the DNA of the antigen [6].  
However, none of these molecular adjuvants has been successful in inducing high titer durable 
antibody or cellular immune responses in humans.  Several studies have used additional non-
traditional adjuvants to improve DNA vaccines.  LT and cholera toxin B (CTB) patches have been 
used at the site of DNA immunization in mice demonstrating increased immune responses [7], [8], 
[9].  CTB has also been given as a mucosal adjuvant with an HIV DNA vaccine and was shown to 
enhance cellular systemic and mucosal genital tract immunity delivery [9].  An aluminum 
adjuvanted DNA vaccine for Toxoplasma gondii had a modest improvement in immunogenicity 
in mice [10].  MPLA has also been used in emulsions with DNA vaccines demonstrating enhance 
immune responses compared to DNA alone [11], [12].  Numerous studies have used various 
liposome or lipid-based nanoparticle formulations for DNA vaccines [3].  Gram-negative bacterial 
ghosts, which contain lipid A, have been used as liposome formulations to deliver DNA vaccines, 
have been shown to induce potent humoral and cellular immune responses in animals [13], [14], 
[15]. 


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Although aluminum salts are widely used and have a proven safety record, the magnitude and 
durability of antibodies to HIV-1 antigens or polyfunctional T cells is low.  In addition, 
combinations of adjuvants with different mechanisms of action may have additive or synergistic 
effects and may affect the magnitude and the quality of the antibody responses more than 
individual adjuvants.  For example, ALF43+Rehydragel® (ALF43A) is an alternative to the highly 
successful, but proprietary, adjuvants such as AS04 (monophosphoryl lipid A (MPLA) adsorbed 
to aluminum salt) used in the GlaxoSmithKline (GSK) FDA-licensed vaccines, Hepatitis B 
(ENGERIX-B) and HPV (CervarixTM).  The RV460 trial builds on the use of non-traditional 
adjuvants to improve the immune response of DNA-based vaccines.  Evaluation of Env-C Plasmid 
DNA plasmid alone, with ALF43, or transcutaneous immunization with dmLT at the site of Env-
C Plasmid DNA immunization will enable a mechanistic description of the adjuvants’ effects on 
immune responses induced by DNA containing HIV Env in humans.  The comparison of 
Rehydragel® and ALF43+Rehydragel® as adjuvants for HIV Env gp145 C.6980 protein will 
further enable mechanistic comparisons.  A Phase 1 study IND to evaluate the safety, tolerability, 
and immunogenicity of an HIV vaccine that tests HIV Env gp145 C.6980 either at a 300 µg HIV 
Env gp145 C.6980 (high dose) or 100 µg (low dose) admixed with aluminum hydroxide adjuvant 
in healthy, HIV-1-uninfected adults in the United States (HVTN 122/Clinicaltrials.gov identifier 
NCT03382418), was submitted to the United States Food and Drug Administration (FDA) by 
DAIDS/NIAID with their network, the HIV Vaccine Trials Network (HVTN). The trial is 
underway and will provide additional immunogenicity and safety information for comparison of 
the adjuvant effects at the completion of both trials. This study of Env-C Plasmid DNA and HIV 
Env gp145 C.6980 protein that is combined with ALF43, tested in combination with various 
adjuvants in the same immunization, will provide exploratory data critical to describing potential 
mechanistic and phenotypic differences with each adjuvant.  
In study arm 7, co-immunization of Env-C Plasmid DNA and HIV Env gp145 C.6980 protein-
based HIV-1 vaccines are administered in the same injection site.  This co-immunization strategy 
using DNA and protein vaccines can improve both humoral and cellular immune antigen-specific 
immune responses over either vaccination alone or both in series [16], [17], [18] and it can even 
improve control of viremia after simian immunodeficiency virus (SIV) challenge in a macaque 
model [18].  Preclinical studies of DNA and protein suggest that colocalizing simultaneous 
administration of the DNA and protein vaccines may optimize the immune response.  In a study 
in nonhuman primates by Jalah et al., [16] the group that received co-administered DNA and 
protein had significantly higher levels of Env-binding antibodies (Abs) and higher avidity that 
persisted compared to the other groups that received either DNA alone or DNA prime with a 
protein boost.  Also, Env-binding Abs and avidity correlated with slower SIV acquisition and in 
addition, cytotoxic CD4+ effector memory inversely correlated with peak viral load [18].  In 
another study, the Haigwood group demonstrated in rabbits that DNA + protein co-administration 
was superior to protein administration alone regarding antibody kinetics, magnitude, avidity, and 
neutralization potency [19].  A recent study with nonhuman primates reported the co-immunization 
of DNA vaccines with recombinant Env proteins mixed together with liposomes containing MPLA 
and imiquimod (TLR4 and TLR7 agonists, respectively) or liposomes containing MPLA and 
QS21 resulted in robust and durable cellular and humoral immune responses that efficiently 
disseminated to mucosal sites and protected against simian immunodeficiency virus (SIV) 
infection [18] Similarly, in another study of co-immunization using DNA and gp120 formulated 
in an oil-in-water emulsion containing a TLR4 agonist also resulted in the highest systemic binding 
and neutralizing antibodies to homologous or heterologous HIV Env as well as the highest Env-


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specific IgG in saliva compared to DNA alone or DNA prime followed by protein boost [16]. In 
addition, the inclusion of DNA in the vaccine significantly increased the longevity of systemic 
humoral immune responses. Previously, the HVTN 096 (NCT01799954) and HVTN 105 
(NCT02207920) studies reported that NYVAC vector or DNA co-immunization with AIDSVAX® 
B/E did not result in increased immune responses.  These studies only used Rehydragel® as an 
adjuvant. The NHP studies discussed above demonstrate that inclusion of a TLR4 agonist in DNA 
protein co-immunization can induce increased and potent immune responses of longer duration. 
Group 7 was included in this study to investigate the immune responses induced using a TLR4 
agonist in liposomes (ALF43) in humans.  
However, the benefits of co-immunization with proteins and vectors have not been widely studied 
in humans.  A recent study demonstrated that co-immunization of a modified vaccinia Ankara 
(MVA) influenza vaccine with a protein influenza vaccine in humans improved both memory T-
cell responses and humoral responses to specific influenza antigens compared to either modality 
alone [20] presumably by enhancing responses to the protein via the intrinsic adjuvant activity of 
the viral vector to induce greater T-cell responses, or by triggering T helper cells in lymph nodes.  
RV460 proposes to characterize antigen-specific responses by transcriptional and antibody 
profiling and Tfh, memory and B-cell functional specificities across peripheral blood, peripheral 
lymph nodes (LN) compartments, gastrointestinal/genitourinary (GI/GU) mucosal immune cells.  
MHRP has performed mucosal and lymph node biopsies in multiple studies.  These include RV398 
and RV419 (mucosal and lymph node in Kenya, Uganda, Tanzania), and RV306 (NCT01931358).  
RV254/SEARCH010 (NCT03032575), RV397, RV398, RV405, RV411, RV412 in Thailand [21], 
[22], [23], [24].  Evaluations of LN architecture and cells before and after vaccination have used 
state-of-the-art assays to probe the relationship among changes in frequency and expansion of 
antigen-specific CD4+ and CD8+ T cells before and after vaccination [25].  Studies of LN 
architecture require intact lymph nodes obtained by excisional LN biopsies.  Additional immune 
assessments will include the relative and absolute frequencies of Tfh cells and B cells and the 
quantification of the expression of inflammatory markers on these cell surfaces.  Malaria groups 
at NIAID and WRAIR, are examining if and how different adjuvants promote CD4+ T cells to 
adopt a suppressive T follicular regulatory (Tfr) phenotype and if that differentiation occurs in LN 
of non-human primates (NHP).  We propose to quantify the kinetics and location of Tfh 
differentiation following vaccination. 
While there is a basic understanding of the induction of long-lived, highly matured antibody 
responses and the varied roles of Tfh cells, dendritic cells, and B cells in this process, it is unknown 
how each cell type determines the quality and function of vaccine-induced immune responses.  
Evaluation of intact LN structure will enable a better understanding of Tfh cell specificity and 
functions, as well as the coordinating mechanisms that lead to long-lived protective B-cell 
responses.  Evaluation of signals involved in B-cell memory formation and phenotyping and 
functional characterization of different types of natural killer (NK) cells will be performed in 
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SCIENTIFIC RATIONALE 
2.2.1 STUDY PRODUCTS AND DOSE JUSTIFICATION 
2.2.1.1 
Env-C Plasmid DNA (HIV-1 gp120 (93MW965.26) DNA)   
The dose of Env-C Plasmid DNA to be used for immunization is 2 mg.  This was based on the 
dose of DNA plasmids (obtained from Dr. Shan Lu, University of Massachusetts Medical School), 
that are being used in PDPHV-201401, the NIAID Sponsored Network study HVTN124 
(NCT03409276).  The 2 mg dose was further selected based on cGMP manufacturing constraints.  
The maximum DNA concentration that could be obtained with precipitation was 4 mg/ml.  The 2 
mg dose is approximately twice that of the low dose (1.2 mg) used in the DP6-001 clinical trial 
[26], [27], which induced significant immune responses to HIV Env. Numerous clinical trials have 
used DNA vaccines in the 1-8 mg range in HIV vaccine clinical trials  [28], [29] [30], [31], [32] 
[33], [34], [35] and other diseases [36]; for reviews see [37], [38], [39]. 
2.2.1.2 
HIV Env gp145 C.6980 Protein 
The dose of HIV Env gp145 C.6980 protein to be used for immunization is 100 μg.  The dose of 
Env protein used in clinical trials has ranged from 5-600 μg [40], [41].  In AVEG 015 
(NCT00001042), 50 μg of gp120 was used [42], [43], [44, 45], whereas in RV144 (NCT00223080) 
300 μg each of gp120 MN and gp120 A244 were used  [46], [47].  The dose of 100 μg matches 
the lower dose of HIV Env gp145 C.6980 used in the HVTN 122 trial (NCT03382418).  Using 
ALF43 and Rehydragel® as an adjuvant, immune responses similar to those observed in 
AVEG015 are expected [45].  Based on the concentration of vialed HIV Env gp145 C.6980 (600 
μg/ml), 100 μg was selected to allow for the mixing of the vaccine components. 
2.2.1.3 
ALF43: Army Liposome Formulation—43% Cholesterol 
The dose of MPLA in ALF43 to be used for immunization is 200 μg.  This was based on previous 
clinical trials with the ALF43 predecessor L(MPLA), in which approximately 200 μg was used in 
a Phase I malaria clinical trial [48] and 11 Phase I prostate [49], [50], [51] or colorectal cancer 
clinical trials [52] and two Phase II prostate clinical trials.  The vaccine induced potent immune 
responses. 
2.2.1.4 
Recombinant Double Mutant Escherichia coli Heat Labile Toxin (dmLT) 
The dose of dmLT to be used in transcutaneous immunization is 50 μg.  This was based on the 
previous clinical trials with transcutaneous immunization using 50 μg of native LT [53], [54], [55], 
[56], [57].  In addition, the use of dmLT in doses up to 50 μg have been used as an antigen and/or 
adjuvant in clinical studies [58], [59], [60], [61]; that was recently reviewed [62]. 
2.2.1.5 
Rehydragel® (Aluminum Hydroxide Fluid Gel) 
The dose of aluminum in Rehydragel® to be used is 500 μg.  This dose was selected to match the 
500 μg dose of aluminum that was used in AVEG015 (NCT00001042) in which ALFA was used 
as an adjuvant [42], [43], [44], [45].  
2.2.2 OVERVIEW OF PRE-CLINICAL STUDY RESULTS 
RV460 evaluates Env-C Plasmid DNA with the HIV Env gp145 C.6980 protein vaccine combined 
with different adjuvants. The adjuvants are dmLT, ALF43, and Rehydragel®.  Supporting 


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information detailing the evaluation of the adjuvants, the Env-C Plasmid DNA and HIV Env gp145 
C.6980 protein vaccines is provided in the Investigators Brochure (IB), Nonclinical Section.  
Each component of the vaccine regimen has both preclinical and clinical data or is part of a larger 
class of products, which, collectively, have been extensively tested.  Although ALF43 has not been 
used in humans, it is a revised formulation of L(MPLA).  ALF43 has reduced levels of 
phospholipids and cholesterol but maintains the same amount of MPLA.  Reports relevant to 
assessing the potential toxicity and the immunogenicity of the combined Env-C Plasmid DNA 
prime-protein boost are described in detail in the IB. WRAIR conducted a preclinical rabbit study 
to evaluate the proposed RV460 vaccine regimen. The purpose of this study was to evaluate the 
magnitude, frequency and durability of immune responses induced by Env-C Plasmid DNA and 
HIV Env gp145 C.6980 protein in combination with the adjuvants ALF43, Alhydrogel, ® and 
dmLT.  The rabbit immunogenicity for RV460 was evaluated with ELISA.  IgG antibodies were 
measured against HIV Env gp145 C.6980, gp120 (C.ZA.1197MB) proteins as well as against 
gp70-V1V2 scaffold antigen.  All groups of rabbits induced high titers of HIV Env gp145 C.6980, 
gp120, and gp70V1V2-specific binding IgG, which were maintained at elevated levels 6 months 
post-immunization.  Co-administration of Env-C Plasmid DNA and HIV Env gp145 C.6980 
protein resulted in titers of 100,000 after just one immunization.  IM Env-C Plasmid DNA 
immunization with dmLT via TCI caused a delay in the induction of Abs until week 16.  
Additionally, neutralizing antibodies against tier 1 viruses were also evaluated.  Sera from all the 
groups had cross-clade Tier 1 neutralizing activities (work in progress).  Neutralization was 
observed only after the HIV Env gp145 C.6980 protein boost and declined from week 24 to week 
32.  However, the Env-C Plasmid DNA/HIV Env gp145 C.6980 protein co-immunization group 
had high neutralization titers starting at week 12, which appeared to be more durable.  Overall, 
Env-C Plasmid DNA prime/boost vaccine regimen in combination with the ALF43, and dmLT 
TCI adjuvants led to the generation of high magnitude durable binding Abs and induced potent 
neutralizing Abs.  
Additionally, toxicity and temperature of all rabbits from RV460 pre-clinical study were evaluated.  
The temperature of rabbits was taken before each immunization, and 6 and 24 hours 
after immunization.  Clinically relevant elevations of temperature were not observed in any of the 
rabbits immunized with the different vaccine regimens.  Blood samples were drawn at Weeks 0, 
4, 8, 12, 16, and 20 from all immunized rabbits for blood chemistry and complete blood cell counts.  
Most of the animals showed blood chemistry levels within normal physiologic range except for a 
few fluctuations in some animals, which was considered normal by the pathologist.  Samples taken 
after Week 8 indicate that there were no abnormal blood chemistry results in any group after the 
last Env-C Plasmid DNA prime was received.  Additionally, blood cell counts were measured in 
pre-immunized animals and at 3 days and again at 1 week after each immunization.  The complete 
blood counts of most rabbits were within the normal physiologic range.  The overall conclusion 
from this rabbit study was that the vaccine formulations were immunogenic, and no safety 
concerns were identified. 
Overall, the vaccine formulations were immunogenic and based on the pyrogenicity and toxicity 
tests conducted side by side with the immunogenicity testing, no abnormal findings or results were 
observed.  Note that ALF43A in combination with a malaria antigen was tested in a GLP rabbit 
pharmacology-toxicology study without adverse findings.   


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See IB for details of these pre-clinical results. 
2.2.3 OVERVIEW OF RELEVANT CLINICAL STUDIES 
Of the five components proposed in the RV460 vaccine regimen, both the Env-C Plasmid DNA 
(IND 17813; HVTN124) and the HIV Env gp145 C.6980 protein (IND 17766; HVTN122) 
vaccines are in clinical Phase 1 trials.  Clinical data on the RV460-specific formulations of 
Rehydragel® or dmLT are published.  The most significant data sets on HIV Env proteins (gp120) 
with Rehydragel® (AIDSVAX® vaccine), [46], [43], [63], [64], come from efficacy trials where 
the product was tested alone or in a prime-boost combination with a canarypox DNA vector 
(RV144) and compared to placebo.  dmLT has been tested as both an antigen and adjuvant in an 
oral vaccine for enterotoxigenic E. coli (ETEC) diarrhea [65], [66], [58].   
2.2.3.1 
Safety and Immunogenicity of the Env-C Plasmid DNA Alone or with an 
HIV Env Protein Boost Vaccine 
DNA plasmid vaccines expressing HIV-1 Env antigens have been tested in multiple clinical studies 
up to 8.0 mg/dose and have demonstrated an acceptable safety profile when administered alone or 
with adjuvanted HIV-1 Env proteins [28], [29], [30], [31], [32], [33], [34], [35] and other diseases 
[36]; for reviews see [37], [38], [39] HIV-1 DNA plasmid vaccines expressing HIV-1 Env antigens 
are safe and relatively well tolerated in humans.  For some HIV-1 DNA Env preparations, pruritus 
or localized delayed-type hypersensitivity (DTH) reactions have occurred as non-serious, low-
grade adverse events (AEs) attributed to the HIV-1 DNA vaccine; but they were not frequent or 
severe enough to halt their respective studies. 
Although the single plasmid of Env-C Plasmid DNA vaccine has not been previously tested in 
humans, a first generation of the Env-C Plasmid DNA vaccine was tested as a multigene, 
polyvalent DNA prime-protein boost HIV-1 vaccine, DP6-001, with the same DNA plasmid 
backbone [26]. 
In this study, each participant received two vaccine components; three sequential inoculations 
using a DNA plasmid vaccine administered either intradermally or intramuscularly followed by 
two sequential inoculations using a protein vaccine. This study involved 2 dose levels of DNA 
vaccines (1.2 mg [Groups A and B]; 7.2 mg [Group C]) expressing five gp120 Env antigens (HIV-
1 clades A, B, C and E) and one Gag antigen (HIV-1 clade C), and a single dose level of the same 
five recombinant expressed gp120 protein vaccines, produced and purified from CHO cells, and 
mixed with QS21 adjuvant at the time of injection.  Additionally, Group C in the previous trial 
received more than 3 times the dose of DNA compared to the 2 mg of Env-C Plasmid DNA 
proposed in RV460.   
After each DNA immunization, Grade 1 or 2 fever was common, occurring in up to 42% of DNA 
vaccine recipients of which Group A (ID) recipients had significantly more frequent injection-site 
erythema after DNA vaccination than Groups B or C (IM).  Local injection site reactions were 
most common (65% of participants) and included Type IV delayed-type hypersensitivity (DTH) 
reactions at prior DNA inoculation sites in 12 of 28 (43%) participants after protein vaccination 
[26].  The erythematous “recall” reactions at prior DNA vaccination sites typically appeared 36 to 
72 hours after injection of the DNA (8 milder reactions) and the protein boost (12 mild to severe 
reactions).   


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Two vasculitis adverse events after the HIV-1 Env protein/QS-21 boost also occurred, which 
halted the study.  One case was leukocytoclastic vasculitis occurring after the protein boost in the 
higher-dose (7.2 mg) DNA prime group.  A second case occurred in a participant whose history of 
Henoch-Schönlein purpura (HSP) as a young adult was not reported before he entered the study.  
This participant experienced Grade 2 fever after DNA vaccination and experienced hepatic and 
renal abnormalities after protein boost that were later recognized as due to recurrence of HSP.  
There have been subsequent HIV-1 DNA prime HIV-1 Env boost vaccination studies (none with 
the adjuvant QS-21) where vasculitis has not been observed again.  Grade 1, 2 or 3 local toxicity 
and occasional Grade 1 or 2 flu-like symptoms has been well documented after vaccinations testing 
QS-21 as an adjuvant. There were mild to moderate dermatological reactions following DNA 
immunization, however, severe reactions occurred after the protein QS21 boost as shown in Study 
DP6-001 [26] suggesting that the severe dermatologic reactions observed after the boost may have 
been due to QS-21 adjuvant.  
In DP6-001, robust cross-subtype HIV-1-specific T-cell response was detected in interferon 
gamma enzyme-linked immunospot assays.  Furthermore, high-titer serum antibody responses 
were detected that recognized a wide range of primary HIV-1 Env antigens and also neutralized 
pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes [67], 
[27].  These findings demonstrated that the DNA prime-protein boost approach is an effective 
immunization method to elicit both humoral and cell-mediated immune responses in humans. 
2.2.3.2 
Safety and Immunogenicity of the HIV Env gp145 C.6980 protein (or other 
HIV-1 Env Protein Vaccines) Alone or with a Plasmid Vector expressing 
HIV-1 Env Antigens as a Prime Vaccination 
The HIV Env gp145 C.6980 protein vaccine has not previously been tested in humans, but the 
protein adjuvanted with Alhydrogel® is undergoing evaluation in an ongoing phase 1 clinical trial 
sponsored by DAIDS under investigational new drug application (IND) 17766 (HVTN122).  
Additionally, HIV-1 Env proteins corresponding to either a full length or a truncated version of 
the HIV-1 Env have been extensively tested in clinical studies and have been safe and well 
tolerated [68], [47], [69], [70].  Specifically, monomeric Env proteins (HIV-1 Env gp120, gp140, 
gp160) have been administered in many clinical trials with aluminum salt adjuvants, either alone 
or as a part of a prime-boost vaccine regimen.   
In a series of studies of HIV-1 gp120 protein vaccines reviewed by Huang et al., the proportion of 
participants who experienced an unsolicited AE after any vaccination was not significantly 
different in vaccine and placebo recipients [71].  Most of all events (95%) in both placebo and 
vaccine recipients were assessed as not related to vaccination.  Pain and tenderness were the most 
frequent local reactions observed.   Vaccine-related local reactions were generally mild and 
resolved within 3 days.  Systemic reactogenicity was observed less frequently and most often as 
transient fatigue and low-grade fever.  2912 SAEs were reported by 2394 study participants 
(14.6%) were observed but there was no statistically significant difference between vaccine 
(14.3%) and placebo recipients (14.9%) [71].  Most SAEs occurred outside the vaccination months 
with less than a 2% SAE rate during the 30 days after treatment.  No deaths have been reported as 
related to HIV-1 Env protein vaccines even when combined with known, relatively more 
reactogenic, or toxic adjuvants such as Incomplete Freund’s adjuvant or the saponin, QS-21 when 
not compounded with other molecules.  


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2.2.3.3 
Safety and Immunogenicity Overview of Army Liposome Adjuvants 
WRAIR has developed various liposomal-based adjuvants for various vaccine antigens including 
Plasmodium falciparum [48], [72], HIV-1 gp120 [43], [44], [45], prostate cancer [73], [50, 51], 
colorectal cancer [52], and Neisseria meningitides [74].  244 participants (72 healthy and 172 with 
cancer) have received the ALF adjuvant, the liposome-containing monophosphoryl lipid A 
L(MPLA) with or without AlOH at different doses ranging from 22 µg to 2,200 µg in different 
formulations with various antigens and administered by different routes.  Reactogenicity events 
were mostly mild and moderate, transient and resolving without sequelae including with the 
highest dose administered.  The most frequent local reactogenicity events recorded include pain 
and tenderness, erythema, and induration.  The most frequent systemic reactogenicity events 
consisted of malaise, myalgia, headache, fever, and nausea.  There were no clinically significant 
laboratory abnormalities.   
See IB WRAIR L(MPLA) safety summary table for details. 
The newer generation of L(MPLA), ALF43, has not been directly tested in humans; however, 
multiple previous clinical trials using its predecessor, L(MPLA) adjuvant formulation with various 
antigens have been conducted and is anticipated to have similar activity and safety attributes.  Both 
the cholesterol and MPLA are now synthetic which will minimize the possibility of the 
introduction of adventitious agents.  ALF43 contains an 11-fold reduction in MPLA relative to the 
L(MPLA) adjuvant evaluated in AIDS Vaccine Evaluation Group (AVEG)015 (NCT00001042; 
biologics investigational new drug application [BB-IND]-5013, biologics master file [BB-MF]-
4292), an adjuvant comparison study.  In that study, 50 μg of a clade B HIV-1 Env gp120 SF2 
vaccine was administered with seven different adjuvants and compared to AlOH given 
intramuscularly without vaccine [43], [44], [45].  The other adjuvants included MPL® (Ribi 
ImmunoChem Research, Inc.), L(MPLA) + AlOH (WRAIR), MF59 (Biocine), MF59 plus MTP-
PE (Biocine), SAF/2 (Biocine), and SAF/2 plus MDP (Syntex Corp., Palo Alto, CA).  110 healthy 
men and women were randomized to the seven different study arms.  The prime vaccination was 
followed by boosts at two and six months; 62 participants received an 18-month boost.  Across the 
seven groups, the most frequent local reactogenicity events were pain and tenderness, and the most 
frequent systemic reactogenicity events were malaise, myalgia, headache, fever, and nausea.   
Three concerning SAEs occurred after completion of the study, two individuals, whom both 
received 2,200 µg L(MPLA) + AlOH, developed multiple sclerosis (MS).   The first is a 49-
year-old female diagnosed with MS almost five years after her last AVEG015 study injection.  The 
participant received the last vaccination on 6 January 1994 and was diagnosed with MS on 7 
December 1998 which is 4 years and 11 months after the last vaccination.     
The second is a 34-year-old male diagnosed with MS 12 years after the last AVEG015 vaccination.  
This case is complicated by the participant’s subsequent enrollments in four other clinical trials 
where he received three unrelated experimental vaccine regimens (RSV, influenza, HCV).  He 
received a diagnosis of MS at the end of the fourth experimental vaccine trial, 12 years after the 
last AVEG015 vaccination.  
A third SAE occurred in a different study evaluating L(MPLA) with a prostate antigen for prostate 
cancer treatment (BB-MF-6205).  After the study, the participant who received the experimental 
prostate cancer vaccine received a mouse monoclonal antibody and then experienced immediate 
anaphylactic shock.  Although the event was assessed as related to the vaccine, the investigators 


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later determined the study participant had developed anti-idiotype antibodies to the mouse 
monoclonal antibody used in the purification of prostate-specific antigen for the study vaccine, 
which then reacted to the monoclonal antibody infusion in the study.  In all other studies, no other 
related SAEs have been reported.  
Immunogenicity of the encapsulated clade B HIV-1 Env gp120 SF2 and L(MPLA) + AlOH in 
AVEG 015 was, in some cases, better than the other regimens [43]. Additionally, preclinical 
studies of ALF using a mouse model demonstrated its superiority over aluminum salt adjuvants 
[75].  Therefore, there is a need to obtain robust safety and immunologic data on ALF adjuvants 
for HIV Env vaccines in humans.  In AVEG015, there were significantly higher IgG antibody 
responses to clade B HIV-1 Env gp120 IIIB and to clade B HIV-1 Env gp120 A244 (Subtype A/E) 
in the liposomal arm than in the AlOH arm (see IB) [45].  Likewise, the vaccines in the liposomal 
arm induced significantly higher and more durable IgG antibody responses to the gp70V1V2 
CaseA2 and to gp70V1V2AE Env proteins observed for the AlOH arm.  These HIV-1 Env antigens 
correlated with a decrease in risk of HIV-1 acquisition in RV144.  In addition, the AlOH-adsorbed 
liposomes containing MPL® (ALF43A) enhanced the magnitude and durability of V1V2-antibody 
responses beyond that observed in any of the previous HIV vaccine efficacy trials. 
2.2.3.4 
Safety and Immunogenicity Overview of Rehydragel® 
AlOH has one of the largest safety databases worldwide, and it is widely accepted as safe.  
Aluminum adjuvants have been in use for over 90 years to increase the efficacy of licensed vaccine 
formulations.  Many Phase 1, 2, 3 and 4 clinical trials involving AlOH demonstrate the excellent 
safety profile of aluminum adjuvants in humans.  There are at least 10 vaccine products approved 
in the United States and approximately 146 worldwide that contain aluminum salts as a vaccine 
additive.   
See IB for a list of 10 US FDA approved vaccines that contain AlOH. 
Aluminum hydroxide (AlOH) and aluminum phosphate have been extensively used as adjuvants 
for HIV-1 vaccines since the 1990s [42], [76], [77], [78]. A review of clinicaltrials.gov has 38 
trials listed in which aluminum is or was being used as an adjuvant for HIV-1 Env antigens [79]. 
The most well know trials were the phase 3 trials with AIDSVAX®. VAX003 [47], VAX004 [68] 
and RV144 [46]. Both VAX003 and VAX004 were conducted in high-risk populations, IV 
injection drug users and men having sex with men, respectively. VAX003 assessed the efficacy of 
AIDSVAX® B/E and VAX004 assessed the efficacy of AIDSVAX® B/B, immunization alone and 
failed to demonstrate vaccine efficacy against the acquisition of HIV-1. Both had high titer, durable 
antibody responses. In contrast, the RV144 trial was conducted in a low-risk cohort that received 
both ALVAC and AIDSVAX® B/E. A modest 31.2% efficacy was observed in RV144. Antibodies 
to gp70V12 were identified as the inverse correlate for the acquisition of HIV-1 [80]. The 
antibodies were of modest titer and waned rapidly. Taken together these data demonstrate that 
aluminum hydroxide can induce high titer antibodies of long duration, but the priming vaccine 
may be critical for antibody titer, duration, and specificity. 
In adults, the most common local adverse events associated with AlOH are pain, redness, and 
swelling at the injection site.  Rarer local reactions are erythema, subcutaneous nodules, contact 
hypersensitivity, and granulomatous inflammation [81], [82].  Administration of a vaccine that 
contains an adjuvant-like AlOH, which forms a depot after injection, results in an inflammatory 


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focus.  The inflammatory focus attracts immune cells and results in a granuloma that contains 
antibody-producing plasma cells [4].  A very rare and unusual neuromuscular disorder called 
macrophagic myofasciitis, which is attributed to the persistence of aluminum salts in muscle, has 
also been reported [83].  The most common systemic AEs are fatigue, headache, myalgia, 
gastrointestinal symptoms, and arthralgia.  Overall, the use of aluminum adjuvants in humans 
poses a minimal risk of AEs.  
See IB for specific study summaries. 
2.2.3.5 
Safety and Immunogenicity Overview of Recombinant Double Mutant 
Escherichia coli Heat Labile Toxin (dmLT; R192G/L211A)  
There is extensive human experience testing heat-labile enterotoxin (E. coli) (LT) - TCI to support 
the assertion that TCI with dmLT at the site of an Env-C Plasmid DNA injection is expected to be 
a potent and safe adjuvant strategy in humans.  In addition, RV460 will test a mutated, inactivated 
LT (dmLT) in which the ability to activate cellular adenylate cyclase has been abolished to 
decrease toxicity.  The proposed RV460 trial will be the first to evaluate the adjuvant dmLT 
delivered by transcutaneous route.  dmLT has previously been used as an adjuvant in several 
clinical trials and as an antigen for exotoxigenic E. coli diarrhea in which it was administered via 
sublingual and intradermal (ID) routes (clinical trial number NCT03548064).  However, the non-
mutated form of LT has been used as an adjuvant with skin patch vaccines (TCI) in multiple 
clinical trials (all these trials are included in tabular form in Investigator Brochure).  TCI is a 
unique needle-free skin patch procedure shown to be safe and well tolerated in humans [53], [54].  
A variety of adjuvants has shown effectiveness in stimulating immunity by TCI such as cholera 
toxin or LT from E. coli. [84].  Transcutaneous application of LT adjuvant was first tested in 
several human clinical trials for ETEC diarrhea or for influenza.  Doses of LT ranged from 25 µg 
to 500 µg placed as a gauze patch on normal skin [53].  When TCI with LT was tested as an 
immune-stimulant patch at the site of influenza immunization in elderly and healthy adults, an 
increase in seroconversion and significant increases in antibody titer to influenza vaccines were 
noted in both younger and elderly adults [85], [56]. 
The LT adjuvant given transcutaneously was also tested in an efficacy field trial for travelers to 
Mexico or Guatemala, but did not meet the efficacy goals [86]; study participants did develop a 4-
fold higher LT antibody titer and the frequency and weight of stool samples were significantly less 
[57]. Of 25 SAEs, 14 occurred in the LT-patch group and 11 in the placebo group, and these events 
in the context of all study AEs did not suggest a safety signal related to the skin application of LT. 
Two deaths in the LT-patch group were a consequence of road traffic accidents.  TCI with LT has 
been safe with usually only mild to moderate side effects that were attributable to the vaccine and 
its application as follows: pruritus, mild redness or rash, and hyperpigmentation at the site of patch 
application in varying incidence and duration depending upon the site preparation method and 
patch used for the trial.  
More recently, transcutaneously administered mutant LT (mLT) (LTR192G) with the ETEC 
adhesion antigen, CfaE, given intradermal was evaluated (BB-INDs 14711 and 15163).  The 
majority of TCI-vaccinated participants exhibited a local vaccine site reaction that was generally 
of mild-to-moderate severity although 68.3% reactions were characterized as erythematous and 
papular and another 13.9% were either erythematous or papular (8.9%) only.  Erythema and 
papules were present after receipt of the first vaccine dose (43.5%), and their frequency appeared 


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to increase after receipt of the second (erythema: 76.7%; papules: 74.4%) and third (erythema: 
75.6%; papules: 63.4%) vaccinations (not statistically significant).  Pigmentary changes at the 
vaccine site were also observed and the majority (47/53; 88.7%) occurred in individuals with a 
preceding papular rash.  Hyperpigmentation occurred in 56.5% of all participants receiving at least 
one vaccine dose and was less common in participants not receiving LTR192G (10.0%) compared 
to 69.4% in those who did (p < 0.001).  Hypopigmentation was only observed in the group 
receiving 10 µg of donor strand complemented CfaE (dscCfaE) co-administered with LTR192G 
(62.5%).  The quality and severity of the skin reactions with transcutaneous may possibly be 
antigen-dependent. 
dmLT has also been evaluated as an oral antigen/adjuvant vaccine in a phase 1 trial for ETEC [58].  
It was safe with no reported side effects and induced both immunoglobulin G (IgG) and 
immunoglobulin A (IgA) antibodies.  In addition, the dmLT still has adjuvant activity by TCI [87]. 
In summary, AEs associated with the use of LT or mLT applied by TCI have generally been 
mild-to-moderate and have included transient local erythema and less frequently 
hypo/hyperpigmentation, rash, and pruritus [55].  The mild-to-moderate hyperpigmentation 
persisted for at least 180 days after vaccination in 150 (18%) of 849 participants who received two 
vaccinations and returned for final assessment in the LT-patch group, compared with none of 842 
participants in the placebo group.  No significant differences in either occurrence or severity of 
systemic AEs (e.g., fever, malaise, headache, and diarrhea) have been observed between the LT-
patch and placebo groups.  To date, there have been no deaths related to the use of LT or dmLT as 
an adjuvant.  Furthermore, dmLT maintains adjuvant activity inducing both humoral and cellular 
immune responses.   
See IB for additional details. 
 
MILITARY RELEVANCE 
The US MHRP mission is to protect the U.S. Military from HIV and improve global health by its 
HIV vaccine research and development, reduce new infections and find a cure.  Presently, HIV is 
a leading cause of death in the global community.  According to reports by UNAIDS, about 36.7 
million people worldwide are infected with HIV-1 as of 2017, with about two million new cases 
in 2017 alone [88][88], [90], [81].  Sub-Saharan Africa carries the greatest burden of HIV, 
accounting for 71% of all HIV infections.  The epidemic, however, is not just isolated to the 
developing world.  As of 2012, there were 50,000 new HIV infections and 1.3 million people living 
with HIV in North America, [89] which is an increase from 1.14 million in 2009 [90].   
Additionally, prevalence continues to increase across Eastern Europe, Central and East Asia and 
the Middle East and North Africa [91].  Unfortunately, a safe and effective HIV vaccine is 
presently an elusive cornerstone of HIV prevention.  The impacts of HIV are widespread and 
include lowered life expectancy, reduced economic growth, and increased health costs.  These 
outcomes ultimately damage social and political cohesion and impede the advancement of global 
health objectives, which poses a risk to national security and the stability of many nation-states. 
In addition to geopolitical concerns, exposure of US Military Forces to high infection rates in both 
developed and developing countries pose a persistent risk to Military personnel.  As reported in 


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2012, there were 366 incident infections in U.S military personnel.  Among Active Duty Forces 
alone, new HIV cases have increased by 22% since 2008, and exposure to the virus, particularly 
among deployed Forces, continues to threaten Force readiness, Force Health Protection, and 
threaten the blood supply.  Furthermore, improved treatment options and the younger age at 
diagnosis, drive higher life expectancy that has substantially increased the cost of ongoing/chronic 
care for Service Members and Beneficiaries.  With an estimated lifetime treatment cost of 
$380,000 per person, the cost to the Department of Defense to provide lifelong therapy for HIV 
infected Service Members (based on 366 cases), estimated to be $140M.  Accordingly, the 
tremendous and destabilizing impacts of HIV across global populations and within the U.S. 
Military demand the implementation of sophisticated scientific, clinical, political, and social 
solutions. 
Through collaboration between USAMRD-A, MHRP, WRAIR and the DAIDS, NIAID, National 
Institutes of Health (NIH), this study aims to add to the growing knowledge and development of 
an HIV vaccine by building upon previous research to assess a potential vaccine regimen thus 
furthering MHRP’s mission. 
 
DESCRIPTION OF KERICHO SITE 
USAMRD-A is a Special Foreign Activity of WRAIR, Silver Spring, Maryland (MD).  USAMRD-
A includes the Kericho, Kenya unit affiliated through a Cooperative Agreement with KEMRI.  The 
unit was activated on a temporary basis in 1969 at the invitation of the Government of Kenya to 
study trypanosomiasis.  The success of that initial venture led to the establishment of a permanent 
activity in 1973.  Over the past 45 years, research has been conducted on malaria, trypanosomiasis, 
leishmaniasis, entomology, HIV/AIDS, Polio, Ebola, Tuberculosis (TB), arboviruses, and other 
infectious diseases, with more than 250 manuscripts published.  
The USAMRD-A HIV Program is a component of MHRP.  In Kenya, the HIV Program field site 
is located at KEMRI/USAMRD-A/Clinical Research Center (CRC) about 260 kilometers 
northwest of Nairobi along the Nairobi-Kisumu highway in the rural Kenyan town of Kericho.  
Kericho’s county population is approximately 752,396 (2009 census), although the larger 
catchment area for both HIV research and treatment is approximately 3 million covering the 
southern portion of the Rift Valley Province.  Kericho is located among the African Highlands in 
the Rift Valley and well known for the growing of tea that forms the rolling “seas of green” within 
the tea plantations.  The primary industry in this region is tea farming, with two large international 
tea companies namely Finlay’s Kenya Ltd and Unilever Tea Kenya Ltd, centered in Kericho 
County Referral Hospital (KCRH).  
Kericho was ranked as the twentieth richest county in Kenya in the 2005/06 National Integrated 
Household Budget Survey.  Income in Kericho comes mainly from agricultural activities, with 
about 40-50% of the population living below the poverty line.  The annual national gross domestic 
product per capita in 2013 averaged 1,245.51 U.S. dollars (USD).  In Kenya, the age of majority 
(i.e. legal age of recognized adulthood or independence) is 18 years.  The Kenyan national literacy 
level according to the Kenya Adult Literacy Survey report published in March 2007 by the Kenya 
National Bureau of Statistics was 64%.  In Kericho, the literacy level is 74.3% in men and 68.9% 
in women.  The government through a network of hierarchical public hospitals, health centers, 
primarily provides the healthcare system in the larger Kericho area (southern Rift Valley) and 


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dispensaries ran by the Kenya Ministry of Health (MoH).  The government health facilities do not 
charge for treatment but levy a small fee for facility maintenance, which can be waived for those 
not able to pay.  In addition to government health care facilities, there are a few faith-based and 
private health care facilities providing services at a small fee.  Access to most health care facilities 
is good given that there exists a reliable public transport system in the region.  
The KEMRI/USAMRD-A CRC is the primary HIV research site in USAMRD-A.  Situated on the 
grounds of the KCRH/MoH, the 55,050 square feet CRC supports both HIV research and care and 
treatment in the southern Rift Valley Province.  The CRC is composed of a clinical area including 
a central pharmacy that can support both vaccine and therapeutic studies as well as provide 
additional non-study medicines for HIV and other non-study related care.  The CRC is a designated 
satellite HIV and TB clinic under the KCRH.  
The CRC laboratory is Kenya’s first and the only College of American Pathologist (CAP) 
accredited laboratory and boasts of a state-of-the-art Information Technology (IT) center that 
supports both HIV research and treatment programs.  Both the CRC pharmacy and laboratory are 
approved by NIAID/DAIDS to participate in DAIDS sponsored vaccine (Site #31352) and 
therapeutics AIDS Clinical Trials Group (ACTG Site #12501); International Maternal Pediatric 
Adolescent AIDS Clinical Trials (IMPAACT site #5121) studies, the only research site with such 
approval in Kenya. 
 
STUDY DESIGN  
The RV460 trial is an exploratory study that will assess the safety, tolerability, and 
immunogenicity of different adjuvant formulations in combination with an Env-C Plasmid DNA 
and HIV Env gp145 C.6980 protein in a prime-boost combination.  Enrolled participants will 
receive 3 doses of Env-C Plasmid DNA as a prime (with or without adjuvants) or admixed with 
HIV Env gp145 C.6980 protein.  The Env-C Plasmid DNA is given alone, formulated with the 
adjuvant ALF43 (Army Liposome Formulation with Monophosphoryl Lipid A (MPLA) and 43% 
Cholesterol) adjuvant, or co-administered with the transcutaneous adjuvant dmLT (E. coli heat 
labile enterotoxin) applied at the injection site. The HIV Env gp145 C.6980 protein boost will be 
mixed with ALF43, Rehydragel® or ALF43 plus Rehydragel®.  
Study groups will be assessed for HIV-1 Env-specific antibodies responses elicited by boosting 
with HIV Env gp145 C.6980 protein adjuvanted with Rehydragel® with or without ALF43.  Group 
7 will assess whether or not the concept of co-delivery of Env-C Plasmid DNA and HIV Env 
gp145 C.6980 protein simultaneously will increase the frequency and magnitude of immune 
responses than Env-C Plasmid DNA given IM alone (after first three vaccinations – Study groups 
1 and 2 or as an Env-C Plasmid DNA IM prime, protein IM boost combination as was observed in 
mice and non-human primates [18], [19, 92, 93].  
Table 1: Study Design 
Group 
n = 
Prime at weeks 0, 4, 12 
Boost at weeks 20, 32, 56 
V 
p 
1 
15 
3 
 Env-C Plasmid DNA (2 mg, 
IM) 
HIV Env gp145 C.6980 protein (100 µg, 
IM)/Rehydragel® (500 µg, IM) 


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Group 
n = 
Prime at weeks 0, 4, 12 
Boost at weeks 20, 32, 56 
V 
p 
2 
15 
3 
Env-C Plasmid DNA (2 mg, 
IM) 
HIV Env gp145 C.6980 protein (100 µg, 
IM)/Rehydragel® (500 µg, IM)/ALF43 
(200 µg, IM) 
3 
15 
3 
Env-C Plasmid DNA (2 mg, 
IM) + dmLT (50 µg, TCI) 
HIV Env gp145 C.6980 protein (100 µg, 
IM)/Rehydragel® (500 µg, IM) 
4 
15 
3 
Env-C Plasmid DNA (2 mg, 
IM) + dmLT (50 µg, TCI) 
HIV Env gp145 C.6980 protein (100 µg, 
IM)/Rehydragel® (500 µg, IM)/ALF43 
(200 µg, IM) 
5 
15 
3 
Env-C Plasmid DNA (2 mg, 
IM)/ ALF43 (200 µg, IM) 
HIV Env gp145 C.6980 protein (100 µg, 
IM)/Rehydragel® (500 µg, IM) 
6 
15 
3 
Env-C Plasmid DNA (2 mg, 
IM)/ALF43 (200 µg, IM) 
HIV Env gp145 C.6980 protein (100 µg, 
IM)/Rehydragel® (500 µg, IM)/ALF43 
(200 µg, IM) 
7 
15 
3 
Env-C Plasmid DNA (2 mg, 
IM)/HIV Env gp145 C.6980 
protein (100 µg, IM)/ALF43 
(200 µg, IM) 
Env-C Plasmid DNA (2 mg, IM)/HIV 
Env gp145 C.6980 protein (100 µg, 
IM)/ALF43 (200 µg, IM)/Rehydragel® 
(500 µg, IM) 
IM= intramuscular, TCI = transcutaneous immunization; ALF43 (Army Liposome Formulation 
with Monophosphoryl Lipid A (MPLA) and 43% Cholesterol); v= Vaccine Recipient; p= 
Placebo 
 
OBJECTIVES 
2.6.1 PRIMARY  
Assess the safety and tolerability (including reactogenicity) of Env-C Plasmid DNA given IM, 
alone, admixed with ALF43 adjuvant, topically applied with dmLT adjuvant, or given with an 
adjuvanted HIV Env gp145 C.6980 protein and followed by adjuvanted HIV Env gp145 
C.6980 protein boost IM immunizations, with or without Env-C Plasmid DNA. 
2.6.2 SECONDARY 
1. Determine whether the adjuvants under study improve the immunogenicity of 
the Env-C Plasmid DNA priming.  
2. Determine whether the addition of ALF43 to the Rehydragel® –HIV Env 
gp145 C.6980 protein boost further improves the immune response to HIV Env 
gp145 C.6980 protein. 
3. Determine whether adjuvants improve humoral responses across vaccination 
regimens.  
4. Evaluate the influence of various adjuvants on cellular immune responses.  
5. Describe mucosal humoral responses across vaccination regimens in 
cervicovaginal and rectal secretions and semen. 


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2.6.3 EXPLORATORY  
1. Characterize B-cell functional specificities for each vaccination regimen. 
2. Characterization of innate immunity. 
3. Assess the innate/gene expression induced across vaccination regimens (DNA 
microarray, RNA sequencing) to compare relative influence of various 
adjuvants in the gene expression profiles of sorted T cell, B cell and innate cell 
subsets. 
4. Perform systems serology analyses.  
2.6.4 SUB-OBJECTIVE   
In participants who elect to undergo lymph node biopsy, characterize HIV-specific responses, T 
cell activation, T follicular helper (Tfh) cell and B cell distribution in intact lymph nodes (excision 
of intact peripheral inguinal lymph node) at weeks 14 and 58. 
 
ENDPOINTS  
2.7.1 PRIMARY  
Safety endpoints will be the solicited AE (local and systemic reactogenicity), and related AEs and 
SAEs. 
2.7.2 SECONDARY 
1. Compare plasma IgG binding antibodies to gp120 and V1V2 in terms of 
magnitude, durability, and area under the curve both after initial DNA priming 
series among groups with differing DNA priming regimens. 
2. Compare plasma IgG binding antibodies to gp120 and V1V2 in terms of 
magnitude, durability, and area under the curve between groups with and 
without Rehydragel® after HIV Env gp145 C.6980 protein boosting. 
3. Characterize plasma IgG and IgA binding antibodies to Env-C Plasmid DNA, 
V1V2, neutralizing antibodies, and non-neutralizing effector functions such as 
ADCC and ADCP with emphasis on RV144 immune correlates of risk of HIV 
acquisition. 
4. Characterize and assess the magnitude of cell-mediated immune responses 
elicited across vaccination regimens including but not limited to antigen-
specific CD4 and CD8 T cell responses and polyfunctionality, induced 
cytokines, chemokines and other inflammatory markers. 
5. Characterize mucosal humoral responses in cervicovaginal and rectal 
secretions and semen including, but not limited to, plasma IgG and IgA 
binding antibodies to HIV-1 Env proteins, IgG and IgA subclass, and 
functional assays. 


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2.7.3 EXPLORATORY 
1. Characterize B-cell functional specificities for each vaccination regimen by 
quantifying antigen-specific responses through B-cell ELISPOT and 
phenotyping the magnitude and activation status of B cell subsets via flow 
cytometry as well as the isolation of monoclonal antibodies from selected 
vaccine recipients. 
2. Characterize innate immunity through quantification of soluble chemokines 
and cytokines and assessing the phenotype and function of cellular innate 
immune subsets such as NK, NKT, and dendritic cells. 
3. Compare relative influence of various adjuvants in the gene expression profiles 
sorted T cell, B cell and innate cell subsets using RNAseq and related methods 
to quantify and compare gene expression from various sorted cell subsets 
among study groups. 
4. Utilizing 
systems 
serology 
analyses, 
link 
various 
immunological 
measurements, including antibody-binding data to antibody effector functional 
assays to evaluate immunologic response patterns or signatures to various 
adjuvants. 
2.7.4 SUB-SET OF PARTICIPANTS THAT ELECT TO UNDERGO LYMPH NODE BIOPSY   
Between each adjuvant group, compare the magnitude and frequency of HIV-1-specific TfH cells 
in total lymph nodes and lymph node follicles, TfH and B cell distribution between intra and 
extrafollicular LN zones, and levels of cellular activation using ICS, immunohistochemistry, 
transcriptional analyses, and related techniques at weeks 14 and 58.  


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 INVESTIGATIONAL PRODUCTS 
 
DESCRIPTION OF STUDY AGENTS 
3.1.1 
 ENV-C PLASMID DNA VACCINE  
The Env-C Plasmid DNA vaccine is supplied as single-dose vials containing 0.9 mL of solution at 
a concentration of 4 mg/mL.  Each 1 mL of solution contains 4 mg of Env DNA vaccine and 9 mg 
of sodium chloride.  The Env DNA vaccine will be stored at ≤-60°C and shipped on dry ice to the 
clinical research site.  When thawed, the study product appears as a clear, colorless liquid.  
3.1.2 HIV-1 ENV GP145 C.6980 
The HIV Env gp145 C.6980 protein vaccine is supplied as single-dose vials containing 0.7 mL of 
solution at a concentration of 600 µg/mL.  The buffer is PBS, pH 7.4.  The HIV Env gp145 C.6980 
protein vaccine will be stored at ≤-65°C and shipped on dry ice to the clinical research site.  When 
thawed, the study product appears as a clear, colorless liquid.    
3.1.3 RECOMBINANT DOUBLE MUTANT ESCHERICHIA COLI HEAT-LABILE TOXIN LT 
(R192G/L211A) (DMLT)  
The dmLT adjuvant will be supplied as a multiple-dose vial (up to two doses can be withdrawn 
from a vial) containing 0.5 mg of lyophilized product.  The lyophilized product was formulated 
at 1 mg/mL in phosphate-buffered saline containing lactose, pH 7.4 and appears as a solid cake, 
consistent, and white to off-white.  Each vial of dmLT will be reconstituted with 0.5 mL of 
sterile water for injection, resulting in a concentration of 1 mg/mL.  The reconstituted product 
appears as a clear, colorless solution.  Filled vials were labeled for storage at ≤ –10°C and are 
stored at –20°C ± 10°C prior to reconstitution.  The dmLT product will be shipped to the clinical 
site on dry ice.  After reconstitution, the dmLT product should be stored at 2-8°C for up to 12 
hours.  A maximum of two doses may be removed from each reconstituted vial for 
administration to study participants.  
3.1.4 ALF43: ARMY LIPOSOME FORMULATION—43% CHOLESTEROL 
The ALF43 adjuvant will be supplied as single-dose vials containing 240 µg of 3D-PHAD® per 
vial.  ALF43 has a phospholipid to 3D-PHAD® molar ratio of 8.8 to 1.  The ALF43 product 
appears as a white to off-white lyophilized powder, which may be in a cake at the bottom of the 
vial or dispersed throughout the vial.  ALF43 is stored at -20°C ± 10°C and shipped to the clinical 
research site on dry ice.  
3.1.5 ALUMINUM HYDROXIDE SUSPENSION—FLUID GEL (REHYDRAGEL®) 
The Rehydragel® adjuvant will be supplied as 3 mL single-dose vials containing 0.7 ± 0.10 mL 
of aluminum suspension at a concentration of 5 ± 1 mg/mL.  The vials are labeled as Aluminum 
Hydroxide suspension fluid gel (adjuvant).  Rehydragel® appears as a white gelatinous precipitate 
in aqueous suspension; opaque.  Rehydragel® will be stored at 2°C to 8°C and will be shipped to 
the clinical research site at the same temperature. 


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3.1.6 0.9% SODIUM CHLORIDE FOR INJECTION (STERILE SALINE) 
0.9% Sodium Chloride for Injection (sterile saline) will be purchased from a commercial vendor 
based on availability at the time required.  The sterile saline will serve as both the diluent and 
placebo for the trial.  Sterile saline will be stored as per the manufacturer’s recommendation.  
Table 2: Study Agents 
Short  
name  
DP 
Composition 
Description 
Developer 
Manufacturer 
Env-C Plasmid 
DNA 
DNA plasmid 
3.6 mg/vial in 
0.9 mL normal 
saline. 
The Env-C Plasmid DNA drug 
product is a DNA plasmid vial 
in single-dose vials at a 
concentration of 4.0 mg/mL 
(3.6 mg/vial, 0.9 mL solution) 
in normal saline. 
University of 
Massachusett
s Medical 
School, MA 
Waisman 
Institute, 
Wisconsin 
HIV Env 
gp145 C.6980  
HIV Env gp145 
C.6980 0.7 
mL/vial at 0.6 
mg/mL in 2.7 
mM potassium 
chloride, 136.9 
mM sodium 
chloride, 1.5 
mM potassium 
phosphate, and 
8.9 mM sodium 
phosphate, pH 
7.4. 
The HIV Env gp145 C.6980 
protein (CO6980v0c22) is 
vialed in PBS, pH 7.4 in single-
dose vials at a concentration of 
600 µg/mL with 0.7 mL/vial. 
MHRP/ 
WRAIR 
ABL through 
Avid, Tustin, 
California 
dmLT 
 
500 µg dmLT 
in lyophilized 
form in sodium 
phosphate 
buffer with 5% 
lactose 
The double mutant heat-labile 
enterotoxin B of E. coli, dmLT 
(R192G/L211A), pH 7.4 is 
lyophilized at 500 µg/vial (0.5 
mg/vial) to be reconstituted 
with 0.5 mL of water for 
injection.  After reconstitution, 
the buffer will be 42.7 mM 
sodium phosphate, 10.7 mM 
potassium phosphate, 82 mM 
sodium chloride and 5% 
lactose. 
Tulane 
University 
GmbH Am 
Pharmapark 
06861 Dessau-
Rosslau 
Germany 


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ALF43 
DMPC: 1.24 
μmol/vial 
DMPG: 0.14 
μmol/vial 
Cholesterol: 
1.03 μmol/vial 
Army Liposome Formulation 
consists of MPLA, 
dimyristoylphosphatidylcholin
e (DMPC), cholesterol (43%), 
and 
dimyristoylphosphatidylglycer
ol (DMPG) All of the lipids are 
synthetic.  The MPLA congener 
that will be used is 3D-PHAD®.  
The final phospholipid 
concentration is 1.15 mM after 
reconstitution.  3D-PHAD®, is at 
concentration of 200 µg/mL of 
the 1.15 mM phospholipid 
liposomes after hydration 
WRAIR 
Avanti Polar 
Lipids/ 
WRAIR 
Rehydragel® 
(Aluminum 
hydroxide 
suspension-- 
fluid gel)  
5 mg/mL 
aluminum in 
H20 
Rehydragel® was vialed at 0.7 
mL ± 0.10 mL volume; 
aluminum concentration of 5 ± 
1mg/mL  
ChemTrade 
New Jersey  
VRC Pilot Plant, 
NIAID, NIH 
See IB for details for individual vaccine component details. 
 
ACQUISITION AND DISTRIBUTION 
Distributed through NIAID Clinical Research Products Management Center (CRPMC)  
• Env-C Plasmid DNA (provided by HJF/MHRP)  
• HIV Env gp145 C.6980 protein (provided by DAIDS/NIAID/NIH)  
• ALF43 (provided by WRAIR) 
• Rehydragel® (provided by the Vaccine Research Center (VRC)/NIAID/NIH)  
• dmLT (provided by PATH, Division of Vaccines)  
• 0.9% sodium chloride for injection will be available through the NIAID CRPMC. 
• Sterile water for injection will be available through the NIAID CRPMC. 
Locally sourced  
• Empty sterile vials will be purchased from a commercial vendor. 
• ECG skin preparation paper (Skin preparation paper) will be purchased from a commercial 
vendor. 
• Sterile 2 x 2-inch, 12 ply cotton gauze pads, individually wrapped will be purchased from 
a commercial vendor. 
• NexcareTM TegadermTM Waterproof Transparent Dressings (3M), 4x4 ¾ inches, 
individually wrapped, will be purchased from a commercial vendor. 
Upon successful completion of protocol registration procedures, the site pharmacist may obtain 
the study products made available to the study site through the NIAID CRPMC by following 
instructions provided in the Pharmacy Guidelines and Instructions for DAIDS Clinical Trials 
Networks. 


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DOSAGE PREPARATION, DISPENSING AND ADMINISTRATION OF STUDY 
PRODUCT 
The vaccines will be given by intramuscular (IM) injection into the deltoid muscle, excluding the 
dmLT adjuvant which is given by TCI.  All products will be combined into one syringe (excluding 
dmLT) for IM injection, i.e., Env-C Plasmid DNA and HIV Env gp145 C.6980/ALF43A for study 
Group 7.  Once combined, the vaccine regimen must be administered as soon as possible, although 
based on the stability data performed in our laboratory (data not shown but a comprehensive report 
was provided to DAIDS), all the vaccine formulations were stable for 24 hours. This is 
significantly more than required time to vaccinate a participant in the clinic. Alternating deltoids 
will be used for subsequent immunizations [63].  Vaccination in contralateral limbs has been 
successfully utilized to achieve prime boost in multiple vaccine trials [63]. Alternating sites 
allowed for better attribution of local reactogenicity reactions. 
The site for injection cleaned with an alcohol wipe before the injection.  Since the interventions 
are vaccines, the concept of a washout period does not apply.  The duration of the interventions is 
unknown, but it is hoped that it would be ten years or longer. 
See IB and Package Inserts for further information on each study product. 
126 healthy men and women between the ages of 18 and 40 years will be randomized to one of 
seven groups: 


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Table 3: Study Groups 
Group 
N 
V/P 
Prime at weeks 0, 4, 12 
Boost at weeks 20, 32, 56 
1 
15/3 
Env-C Plasmid DNA (2 mg, 
IM) 
HIV Env gp145 C.6980 (100 µg, 
IM)/Rehydragel® (500 µg, IM) 
2 
15/3 
Env-C Plasmid DNA (2 mg, 
IM) 
HIV Env gp145 C.6980 (100 µg, 
IM)/Rehydragel® (500 µg, IM) / ALF43 
(200 µg, IM) 
3 
15/3 
Env-C Plasmid DNA (2 mg, 
IM) + dmLT (50 µg, TCI) 
HIV Env gp145 C.6980 (100 µg, 
IM)/Rehydragel® (500 µg, IM) 
4 
15/3 
Env-C Plasmid DNA (2 mg, 
IM) + dmLT (50 µg, TCI) 
HIV Env gp145 C.6980 (100 µg, 
IM)/Rehydragel® (500 µg, IM) / ALF43 
(200 µg, IM) 
5 
15/3 
Env-C Plasmid DNA (2 mg, 
IM) / ALF43 (200 µg, IM) 
HIV Env gp145 C.6980 (100 µg, 
IM)/Rehydragel® (500 µg, IM) 
6 
15/3 
Env-C Plasmid DNA (2 mg, 
IM) / ALF43 (200 µg, IM) 
HIV Env gp145 C.6980 (100 µg, 
IM)/Rehydragel® (500 µg, IM) / ALF43 
(200 µg, IM) 
7 
15/3 
Env-C Plasmid DNA (2 mg, 
IM) /HIV Env gp145 C.6980 
(100 µg, IM)/ALF43 (200 µg, 
IM) 
Env-C Plasmid DNA (2 mg, IM) /HIV 
Env gp145 C.6980 (100 µg, IM)/ALF43 
(200 µg, IM)/Rehydragel® 500 µg, IM) 
IM= intramuscular, TCI = transcutaneous immunization; ALF43 (ALF43 Army Liposome 
Formulation with Monophosphoryl Lipid A (MPLA) and 43% Cholesterol the 3D-PHAD® dose 
is 200 µg); V= Vaccine Recipient; P= Placebo; Rehydragel® dose is 500 µg aluminum.  
3.3.1 PREPARATION OF INVESTIGATIONAL PRODUCTS 
The clinical research pharmacist will prepare all doses for administration in the pharmacy and 
dispense to the clinic for administration.  The pharmacist must be proficient in the preparation of 
products requiring aseptic technique under a pharmacy biological safety cabinet/isolator.  Local 
regulations and site institutional policies and procedures for use of protective equipment, such as 
gloves, gowns, face masks and safety glasses, must be followed. 
To preserve blinding, the pharmacist will prepare placebo syringes in the same manner as active 
vaccine syringes.  Upon completion of placebo syringe preparation, the pharmacist will hold the 
prepared syringes in the pharmacy for the same length of time as it would take to prepare and 
dispense active vaccine syringes.  Before releasing prepared study product to the clinic, the 
pharmacist will place an overlay on all syringes to maintain blinding (refer to protocol sections 
3.3.1 and 3.3.3) 


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3.3.1.1 
Env-C Plasmid DNA 
One vial of Env-C Plasmid DNA and 0.9% sodium chloride for injection will be needed to prepare 
the dose.  One vial of Env-C Plasmid DNA will be removed from the -70°C or colder freezer and 
allowed to thaw completely at room temperature (15-30°C, approximately 15 minutes).  One vial 
of 0.9% sodium chloride for injection will be removed from storage. 
When thawed, using aseptic technique, the pharmacist will add 0.9 mL of 0.9% sodium chloride 
for injection to the Env-C Plasmid DNA vial using a 22-25-gauge needle and a 1-mL syringe.  The 
diluted Env-C Plasmid DNA vial will be swirled by hand for 1-2 minutes.  Using a 3-mL syringe 
and a 22-25 gauge needle, 1 mL of the diluted product will be withdrawn from the vial for study 
participant administration.  The pharmacist will apply an overlay to the syringe to maintain 
blinding. 
The syringe should be labeled as “Env-C Plasmid DNA 2 mg or Placebo 1 mL”, as well as 
“Administer IM in deltoid”.  The study product preparation and expiration times will also be listed 
on the prepared participant-specific study product label.  The syringe containing the study product 
should be bagged for transport to the clinic where it will be administered.  The study product 
should be administered within 4 hours of preparation. 
Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.1.2 
Placebo for Env-C Plasmid DNA 
Using aseptic technique, the pharmacist will withdraw 1 mL of 0.9% sodium chloride for injection 
into a 3-mL syringe.  The pharmacist will apply an overlay to the syringe to maintain blinding. 
The syringe should be labeled as “Env-C Plasmid DNA 2 mg or Placebo 1 mL”, as well as 
“Administer IM in deltoid”.  The study product preparation and expiration times will also be listed 
on the prepared study product label.  The syringe containing the study product should be bagged 
for transport to the clinic where it will be administered.  The study product should be administered 
within 4 hours of preparation. 
Any unused portion of entered vials or expired prefilled syringes should be disposed of in 
accordance with institutional or pharmacy policy. 
3.3.1.3 
dmLT 
One vial of dmLT, cold sterile water for injection, 0.9% sodium chloride for injection, and one 
empty sterile vial will be needed to prepare the dose.  The dmLT vial will be removed from the -
20℃ freezer.  The sterile water for injection, the 0.9% sodium chloride for injection, and the empty 
sterile vial will be removed from storage and then, using aseptic technique and a 22-25-gauge 
needle and a 1 mL syringe, the dmLT vial will be reconstituted with 0.5 mL of cold sterile water 
for injection.  The resulting concentration will be 1 mg/mL.  The dmLT vial will be gently swirled 
and inverted by hand for approximately 10 times to fully suspend the contents.  Following 
resuspension, the vial will be held at room temperature for 10-15 minutes to ensure full dissolution.  
The vial will be visually inspected to ensure the absence of clumps of undissolved powder. After 
reconstitution, a maximum of 2 doses may be removed from each reconstituted vial of dmLT for 


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administration to study participants. The reconstituted dmLT vial should be stored at 2-8°C for a 
maximum of 12 hours.  Discard the reconstituted vial after this time.   
Using a 22-25-gauge needle and a 3 mL syringe, 1.9 mL of cold 0.9% sodium chloride will be 
added to an empty sterile vial. Reconstituted dmLT will be swirled again by hand for 1-2 minutes. 
Then using a 0.3 mL ultra-fine insulin syringe with a 30-gauge ½-inch needle or a 0.5 mL syringe, 
0.1 mL of the reconstituted dmLT solution will be withdrawn from the vial and added to the vial 
containing 1.9 mL of cold 0.9% sodium chloride to bring the concentration to 50 μg/mL. The vial 
will be swirled by hand for 1 to 2 minutes.  Using a 22-25-gauge needle and a 3 mL syringe, 1 mL 
of the solution will be withdrawn from the vial for study participant administration.   
The syringe should be labeled as “dmLT 50 µg or Placebo 1 mL”, as well as “Administer by TCI”.  
The study product preparation and expiration times will also be listed on the prepared study 
product label. The syringe containing the study product should be bagged for transport to the clinic 
where it will be administered. The study product must be placed in the refrigerator and removed 
for administration when clinic confirms participant is ready. The study product should be 
administered within 15 minutes of preparation. Any unused portion of vials or expired prefilled 
syringes should be disposed of in accordance with institutional or pharmacy policy. 
3.3.1.4 
Placebo for dmLT 
Using aseptic technique, the pharmacist will withdraw 1 mL of 0.9% cold sodium chloride for 
injection, previously stored at 2 – 8 oC, into a 3 mL syringe. The syringe should be labeled as 
“dmLT 50 µg or Placebo 1 mL”, as well as “Administer by TCI”.  The study product preparation 
and expiration times will also be listed on the prepared study product label. The syringe containing 
the study product should be bagged for transport to the clinic where it will be administered. The 
study product must be placed in the refrigerator and removed for administration when clinic 
confirms participant is ready. The study product should be administered within 15 minutes of 
preparation. 
Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.1.5 
Env-C Plasmid DNA + ALF43 
One vial of Env-C Plasmid DNA, one vial of ALF43, and 0.9% sodium chloride for injection will 
be needed to prepare the dose.  One vial of Env-C Plasmid DNA will be removed from the -70℃ 
or colder freezer and allowed to thaw completely at room temperature (15-30°C, approximately 
10-15 minutes).  One vial of ALF43 will be removed from the -20℃ freezer and allowed to 
equilibrate to room temperature (15-30°C approximately 10-15 minutes). 
Once equilibrated to room temperature, using aseptic technique with a 22-25-gauge needle and a 
1-mL syringe, 0.6 mL of 0.9% sodium chloride for injection will be added the ALF43 vial.  The 
ALF43 vial will be mixed using a Vortex mixer set at 2500 RPM for 5 minutes.  The vial will be 
incubated at room temperature for 5 minutes.    
When the Env-C Plasmid DNA vial is thawed, the pharmacist will swirl by hand for 1-2 minutes. 
Then, using aseptic technique, the pharmacist will add 0.6 mL of Env-C Plasmid DNA to the vial 
containing hydrated ALF43 using a 22-25-gauge needle and a 1-mL syringe.  The Env-C Plasmid 


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DNA + ALF43 vial will be gently swirled by hand for 1-2 minutes.  Then, using a 3-ml syringe 
and a 22-25-gauge needle, 1 mL of the solution will be withdrawn from the vial for study 
participant administration. 
The syringe should be labeled as “Env-C Plasmid DNA 2 mg+ALF43 200 μg 3D-PHAD or 
Placebo 1 mL”, as well as “Administer IM in deltoid”.  The study product preparation and 
expiration times will also be listed on the prepared study product label.  The syringe containing 
study product should be bagged for transport to the clinic where it will be administered.  The study 
product should be administered within 4 hours of preparation. 
Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.1.6 
Placebo for Env-C Plasmid DNA + ALF43 
Using aseptic technique, the pharmacist will withdraw 1 mL of 0.9% sodium chloride for injection 
into a 3-mL syringe.  
The syringe should be labeled as “Env-C Plasmid DNA 2 mg+ALF43 200 μg 3D-PHAD or 
Placebo 1 mL”, as well as “Administer IM in deltoid.”  The study product preparation and 
expiration times will also be listed on the prepared study product label.  The syringe containing 
the study product should be bagged for transport to the clinic where it will be administered.  The 
study product should be administered within 4 hours of preparation. 
Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.1.7 
Env-C Plasmid DNA + HIV Env gp145 C.6980 + ALF43 
One vial of Env-C Plasmid DNA, one vial of ALF43, one vial of HIV Env gp145 C.6980 and 0.9% 
sodium chloride for injection will be needed to prepare the dose.  One vial of Env-C Plasmid DNA 
and one vial of HIV Env gp145 C.6980 will be removed from the -70°C or colder freezer and 
allowed to thaw completely at room temperature (15-30°C, approximately 10-15 minutes).  One 
vial of ALF43 will be removed from the -20℃ freezer and allowed to equilibrate to room 
temperature (15-30°C, approximately 10-15 minutes).  0.9% sodium chloride for injection will be 
removed from storage.  Once equilibrated to room temperature, using aseptic technique and a 22-
25-gauge needle and a 1 mL syringe, 0.4 mL of 0.9% sodium chloride for injection will be added 
to the ALF43 vial. The hydrated ALF43 vial will be mixed using a Vortex mixer set at 2500 RPM 
for 5 minutes.  
When the HIV Env gp145 C.6980 vial is thawed, the pharmacist will swirl by hand for 1-2 minutes.  
Then, using aseptic technique, the pharmacist will add 0.2 mL of the HIV Env gp145 C.6980 to 
the vial containing the hydrated ALF43 using a 22-25-gauge needle and a 1 mL syringe. The HIV 
Env gp145 C.6980 + ALF43 vial will be swirled gently with a vortex mixer set at 250 RPM for 2 
minutes.  
When the Env-C Plasmid DNA vial is thawed, the pharmacist will swirl by hand for 1–2 minutes.  
Then, using aseptic technique, the pharmacist will add 0.6 mL of Env-C Plasmid DNA to the vial 
containing the HIV Env gp145 C.6980 + ALF43 mixture using a 22-25-gauge needle and a 1 mL 


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syringe. The vial containing Env-C Plasmid DNA + HIV Env gp145 C.6980 + ALF43 will be 
swirled gently with a vortex mixer set at 250 RPM for 5 minutes. Using a 3-mL syringe and a 22-
25-gauge needle, 1mL of this solution will be withdrawn from the vial for study participant 
administration. 
The syringe should be labeled as “Env-C Plasmid DNA 2mg+HIV Env gp145 C.6980 100 μg 
+ALF3 200 μg 3D-PHAD or Placebo 1ml”, as well as “Administer IM in deltoid”.  The study 
product preparation and expiration times will also be listed on the prepared study product label.  
The syringe containing the study product should be bagged for transport to the clinic where it will 
be administered.  The study product should be administered within 4 hours of preparation. 
Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.1.8 
Placebo for Env-C Plasmid DNA + HIV Env gp145 C.6980 Protein + ALF43 
Using aseptic technique, the pharmacist will withdraw 1 mL of 0.9% sodium chloride for injection 
into a 3-mL syringe.  
The syringe should be labeled as “Env-C Plasmid DNA 2 mg + HIV Env gp145 C.6980 100 µg + 
ALF43 200 μg 3D-PHAD or Placebo 1 mL”, as well as “Administer IM in deltoid”.  The study 
product preparation and expiration times will also be listed on the prepared study product label.  
The syringe containing the study product should be bagged for transport to the clinic where it will 
be administered.  The study product should be administered within 4 hours of preparation. 
Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.1.9 
HIV Env gp145 C.6980 Protein + Rehydragel® 
One vial of HIV Env gp145 C.6980 protein, one vial of Rehydragel®, and 0.9% sodium chloride 
for injection will be needed to prepare the dose.  One vial of HIV Env gp145 C.6980 protein will 
be removed from the -70℃ or colder freezer and allowed to thaw completely at room temperature 
(15-30°C, approximately 15 minutes).  One vial of Rehydragel® will be removed from the 
refrigerator and allowed to equilibrate to room temperature (15-30°C approximately 10-15 
minutes) and then vortexed at 3200 RPM for 30 seconds.  0.9% sodium chloride for injection will 
be removed from storage.   
Once the Rehydragel® vial (5 mg/mL) is equilibrated to room temperature, using aseptic technique 
and a 22-25-gauge needle and a 1-mL syringe, the pharmacist will add 0.85 mL of 0.9% sodium 
chloride for injection to the vial.  The resulting dilute Rehydragel® suspension will have a 
concentration of 2.26 mg/mL.  Swirl by hand for 1 to 2 minutes, then using a new 22-25-gauge 
needle and a 1-mL syringe, 0.4 mL of dilute Rehydragel® (2.26 mg/mL) will be added to an empty 
sterile vial.  
When the HIV Env gp145 C.6980 vial is thawed, swirl by hand for 1–2 minutes.  Then, using 
aseptic technique with a 22-25-gauge needle and a 1-mL syringe, the pharmacist will withdraw 
0.3 mL of the HIV Env gp145 C.6980 solution and add it to the sterile vial containing 0.4 mL of 
diluted Rehydragel. With a 22-25-gauge needle and a 3-mL syringe, the pharmacist will add 1.1 


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mL of 0.9% sodium chloride for injection to the diluted Rehydragel + HIV Env gp145 C.6980 vial 
to bring the volume to 1.8 mL. The vial will be swirled by hand for 1–2 minutes and then will be 
incubated at 15-30°C for 10 minutes.  After incubation, the vial will be swirled by hand for 1–2 
minutes.  Using a 3-mL syringe, 1 mL of the formulation will be withdrawn from the vial for study 
participant administration.    
The syringe should be labeled as “HIV Env gp145 C.6980 100 µg + Rehydragel® 500 µg or 
Placebo 1 mL”, as well as “Administer IM in deltoid.”  The study product preparation and 
expiration times will also be listed on the prepared study product label.  The syringe containing 
the study product should be bagged for transport to the clinic where it will be administered.  The 
study product should be administered within 4 hours of preparation. 
Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.1.10 
Placebo for HIV Env gp145 C.6980 Protein + Rehydragel® 
Using aseptic technique, the pharmacist will withdraw 1 mL of 0.9% sodium chloride for injection 
into a 3-mL syringe.  
The syringe should be labeled as “HIV Env gp145 C.6980 100 µg + Rehydragel® 500 µg or 
Placebo 1 mL”, as well as “Administer IM in deltoid”.  The study product preparation and 
expiration times will also be listed on the prepared study product label.  The syringe containing 
the study product should be bagged for transport to the clinic where it will be administered.  The 
study product should be administered within 4 hours of preparation. 
Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.1.11 
HIV Env gp145 C.6980 Protein + ALF43 + Rehydragel® 
One vial of HIV Env gp145 C.6980, one vial of ALF43, one vial of Rehydragel® and 0.9% sodium 
chloride for injection will be needed to prepare the dose.  One vial of HIV Env gp145 C.6980 will 
be removed from the -70°C or colder freezer and allowed to thaw completely at room temperature 
(15-30°C, approximately 10-15 minutes).  One vial of ALF43 will be removed from the -20°C 
freezer and allowed to equilibrate to room temperature (15-30°C, approximately 10-15 minutes).  
One vial of Rehydragel® will be removed from the refrigerator and allowed to equilibrate to room 
temperature (15-30°C, approximately 10-15 minutes) and then shaken to resuspend the aluminum 
hydroxide.  0.9% sodium chloride for injection will be removed from storage. Once the 
Rehydragel® vial (5 mg/mL) is equilibrated to room temperature, it should be vortexed at 3200 
RPM for 30 seconds, then using aseptic technique and a 22-25-gauge needle and a 1 mL syringe, 
the pharmacist will withdraw 0.3mL of the suspension and add it to an empty sterile vial.   
When the HIV Env gp145 C.6980 vial is thawed, the pharmacist will swirl by hand for 1–2 
minutes.  Then, using a 22-25-gauge needle and a 1-mL syringe, the pharmacist will withdraw 0.5 
mL of the solution and add it to the vial containing 0.3 mL of undiluted Rehydragel®.  Using a 
22-25-gauge needle and a 1-mL syringe, the pharmacist will add 0.2 mL of 0.9% sodium chloride 
for injection to the vial containing HIV Env gp145 C.6980 + Rehydragel®, to bring the volume to 
1 mL.  The vial will be swirled by hand for 1 to 2 minutes and then will be incubated at 15-30°C 


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for 10 minutes.  After incubation, the vial will be swirled by hand for 1–2 minutes.  Using aseptic 
technique, the pharmacist will withdraw 0.4 mL of the HIV Env gp145 C.6980 + Rehydragel® 
using a 22-25-gauge needle and a 1-mL syringe and will add it to the vial containing ALF43.  
Using a 22-25-gauge needle and a 1-mL syringe, the pharmacist will add 0.8 mL of 0.9% sodium 
chloride for injection to the vial containing HIV Env gp145 C.6980 + Rehydragel® + ALF43, to 
bring the volume to 1.2 mL. The vial will be mixed using a Vortex mixer set at 250 RPM for 2 
minutes. Using a 3-mL syringe and a 22-25-gauge needle, 1 mL of the formulation will be 
withdrawn from the vial for study participant administration.  
The syringe should be labeled as “HIV Env gp145 C.6980 100 µg+ALF43 200 μg 3D-PHAD + 
Rehydragel® 500 µg or Placebo 1 mL”, as well as “Administer IM in deltoid”.  The study product 
preparation and expiration times will also be listed on the prepared study product label.  The 
syringe containing the study product should be bagged for transport to the clinic where it will be 
administered.  The study product should be administered within 4 hours of preparation. 
Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.1.12 
Placebo for HIV Env gp145 C.6980 Protein + ALF43 + Rehydragel® 
Using aseptic technique, the pharmacist will withdraw 1 mL of 0.9% sodium chloride for injection 
into a 3-mL syringe.  
The syringe should be labeled as “HIV Env gp145 C.6980 100 µg+ALF43 200 μg 3D-PHAD+ 
Rehydragel® 500 µg or Placebo 1 mL”, as well as “Administer IM in deltoid”.  The study product 
preparation and expiration times will also be listed on the prepared study product label.  The 
syringe containing study product should be bagged for transport to the clinic where it will be 
administered.  The study product should be administered within 4 hours of preparation. 
Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.1.13 
Env-C Plasmid DNA + HIV Env gp145 C.6980 Protein + ALF43 + 
Rehydragel® 
One vial of Env-C Plasmid DNA, one vial of HIV Env gp145 C.6980, one vial of ALF43, one vial 
of Rehydragel® and 0.9% sodium chloride for injection will be needed to prepare the dose.  One 
vial of Env-C Plasmid DNA and one vial of HIV Env gp145 C.6980 will be removed from the-
70°C or colder freezer and allowed to thaw completely at room temperature (15-30°C, 
approximately 10-15 minutes). One vial of ALF43 will be removed from the -20°C freezer and 
allowed to equilibrate to room temperature (15-30°C, approximately 10-15 minutes). One vial of 
Rehydragel® will be removed from the refrigerator and allowed to equilibrate to room temperature 
(15-30°C, approximately 10-15 minutes) and then vortexed at 3200 RPM for 30 seconds.  0.9% 
sodium chloride for injection will be removed from storage. 
The pharmacist will swirl the Rehydragel® vial by hand for 1 to 2 minutes, then using aseptic 
technique and a 22-25-gauge needle and a 1 mL syringe, the pharmacist will withdraw 0.3 mL of 
undiluted Rehydragel® (5 mg/mL) and add it to an empty sterile vial.  


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When the HIV Env gp145 C.6980 vial is thawed, the pharmacist will swirl by hand for 1–2 
minutes.  Then, using aseptic technique with a 22-25-gauge needle and a 1-mL syringe, the 
pharmacist will withdraw 0.5 mL of the HIV Env gp145 C.6980 solution and add it to the vial 
containing 0.3 mL of undiluted Rehydragel®.  Using a 22-25-gauge needle and a 1-mL syringe, 
the pharmacist will add 0.2 mL of 0.9% sodium chloride for injection to the vial containing 
Rehydragel® + HIV Env gp145 C.6980 to bring the volume to 1 mL. The vial will be swirled by 
hand for 1–2 minutes and then will be incubated at room temperature (15-30°C) for 10 minutes.  
After incubation, the vial will be swirled by hand for 1–2 minutes. 
Using aseptic technique, the pharmacist will withdraw 0.4 mL of the HIV Env gp145 C.6980 + 
Rehydragel® using a 22-25-gauge needle and a 1-mL syringe and will add it to the vial containing 
ALF43.  The vial will be mixed using a Vortex mixer set at 2500 RPM for 5 minutes.  
The pharmacist will swirl by hand for 1-2 minutes the thawed Env-C Plasmid DNA vial. Then, 
using aseptic technique with a 22-25-gauge needle and a 1 mL syringe, the pharmacist will 
withdraw 0.6 mL of Env-C Plasmid DNA from the thawed Env-C Plasmid DNA vial and will add 
it to the vial containing HIV Env gp145 C.6980 + Rehydragel® + ALF43. Using a 22-25-gauge 
needle and a 1 mL syringe, the pharmacist will add 0.2 mL of 0.9% sodium chloride for injection 
to the HIV Env gp145 C.6980 C.6980 + Rehydragel® + ALF43 + Env-C Plasmid DNA vial, to 
bring the volume to 1.2 mL. The vial will be mixed using a Vortex mixer set at 250 RPM for 2 
minutes.  
Using a 3 mL syringe and a 22-25 gauge needle, 1 mL of the formulation will be withdrawn from 
the vial for study participant administration. 
The syringe should be labeled as “Env-C Plasmid DNA 2 mg+ HIV Env gp145 C.6980 100 µg+ 
ALF43 200 μg 3D-PHAD + Rehydragel® 500 µg or Placebo 1 mL”, as well as “Administer IM 
in deltoid”. The study product preparation and expiration times will also be listed on the prepared 
study product label.  The syringe containing the study product should be bagged for transport to 
the clinic where it will be administered.  The study product should be administered within 4 hours 
of preparation. 
Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.1.14 
Placebo for Env-C Plasmid DNA + HIV Env gp145 C.6980 Protein + ALF43 
+ Rehydragel® 
Using aseptic technique, the pharmacist will withdraw 1 mL of 0.9% sodium chloride for injection 
into a 3-mL syringe.  
The syringe should be labeled as “Env-C Plasmid DNA 2 mg+ HIV Env gp145 C.6980 100 µg+ 
ALF43 200 μg 3D-PHAD + Rehydragel® 500 µg or Placebo 1 mL”, as well as “Administer IM 
in deltoid”.  The study product preparation and expiration times will also be listed on the prepared 
study product label.  The syringe containing the study product should be bagged for transport to 
the clinic where it will be administered.  The study product should be administered within 4 hours 
of preparation. 


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Any unused portion of vials or expired prefilled syringes should be disposed of in accordance with 
institutional or pharmacy policy. 
3.3.2 PRODUCTS USED FOR DOSE PREPARATION AND ADMINISTRATION 
3.3.2.1 
Sterile Water for Injection 
Sterile water for injection will be purchased from a commercial vendor based on availability at the 
time required.  Sterile water for injection will be used for hydration of the dmLT.  Sterile water for 
injection will be stored as per the manufacturer’s recommendation.  
3.3.2.2 
0.9% Sodium Chloride for Injection 
0.9% sodium chloride for injection (sterile saline) will be purchased from a commercial vendor.  
The sterile saline will serve as both the diluent and placebo for the trial.  Sterile saline will be 
stored as per the manufacturer’s recommendation. 
3.3.2.3 
Empty Sterile Vials 
Empty, sterile, depyrogenated, clears glass vials will be used to mix study products.  The vials will 
be purchased from a commercial vendor based on availability at the time required.  The vials will 
be made of Type I borosilicate glass, with butyl stoppers and aluminum seals.  The vials will be 
stored as per the manufacturer’s recommendation. 
3.3.2.4 
ECG Skin Preparation Paper 
ECG skin preparation paper (skin preparation paper) will be purchased from a commercial vendor 
and stored as per the manufacturer’s recommendation.  It will be used to prepare the skin prior to 
patch application. 
3.3.2.5 
Sterile 2 x 2-inch, 12 Ply Gauze Pad 
Sterile 2 x 2-inch, 12-ply cotton gauze pads, individually wrapped will be purchased from a 
commercial vendor and stored as per the manufacturer’s recommendation. 
3.3.2.6 
Nexcare™ Tegaderm™ Waterproof Transparent Dressing  
Nexcare™ Tegaderm™ waterproof transparent dressing (3M), 4x4 ¾ inches, individually 
wrapped, will be purchased from a commercial vendor and stored as per the manufacturer’s 
recommendation.  
3.3.3 LABELLING TO PRESERVE BLINDING 
The participants, the clinical staff and the Principal Investigator will be blinded to treatment 
allocation.  The site pharmacist will maintain the randomization code and complete assignments 
of participants according to the randomization allocation.   
The study statistician or DCAC will prepare a randomization list for distribution via password-
protected email to the pharmacist.  This will include de-identified participant study numbers, 
treatment assignments, and randomization codes. 
Site pharmacists will prepare all doses in the pharmacy and then deliver to the clinic for 
administration.  The pharmacist will apply an overlay to the dosing syringes before applying the 


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syringe label to prevent possible unblinding if the appearance of the vaccines differs. The study 
assignment will not appear on any label or document leaving the pharmacy.  The syringes will be 
labeled as follows: 
• Participant identifier 
• Study product name/placebo 
• Dose and volume of all study products/placebo in the syringe 
• Route (IM or TCI) 
• Preparation date and time 
• Expiration date and time 
• Any additional information required by the jurisdiction 
3.3.4 EXPERIMENTAL VACCINATION ADMINISTRATION 
The investigator will determine which arm the injection or TCI will be administered for the first 
dose and will use the contralateral arm alternating with each subsequent dose.  The investigator 
will assess the planned vaccination site and determine if it is appropriate and allows for adequate 
post- vaccination assessment.   If the participant has scarring, tattoos, or marks that would obscure 
assessment of the site, the investigator may determine to adjust the planned vaccination area; this 
could mean that the ipsilateral site is ideal.   This data is captured in the case report forms as well 
as in the participant’s study chart source document. 
The injection site on the arm to be used for immunization will be gently rubbed five times with an 
alcohol pad. The injection site will be gently abraded with approximately 10 swipes of an ECG 
Skin Preparation Paper, M4606A (Philips). The injection site will then be wiped again with an 
alcohol pad [57].  (The purpose of these procedures is to increase the permeability of the skin. The 
alcohol wipe extracts lipids from the dead skin cell on the surface of the skin and loosens the dead 
cells. The skin preparation paper removes dead skin cells from the surface.) Next the Env-C 
Plasmid DNA will be injected IM at this site. In parallel, a sterile 2 x 2-inch, 12 ply gauze pad will 
be placed on the adhesive side of a TegadermTM waterproof transparent dressing (4 x 4 ¾ inches). 
Using a 22-25-gauge needle and a 3-mL syringe, 1 mL of the diluted dmLT will be added to the 
gauze pad. This gauze pad-TegadermTM dressing will be placed at the site of Env-C Plasmid DNA 
injection of the volunteer [56], [85]. Similarly, for the placebo recipients, saline will be applied to 
the pad instead of diluted dmLT. Site investigators will be trained on the site preparation and 
application prior to the start of the trial. Participants will wear the patch for 6 hours ±2 hours (range 
4-8 hours) after application. The participants will remove the patch and record the time on the 
diary card. 
 
STUDY PRODUCT ACCOUNTABILITY  
Upon receipt at the site pharmacy, the products will be stored in and dispensed by the 
Investigational Pharmacy.  The Food and Drug Administration (FDA) requires accounting for the 
disposition of all investigational products. The Investigator is responsible for ensuring that a 
current record of product disposition is maintained, and the product is dispensed only at the site 
by authorized personnel as required by applicable regulations and guidelines. Records of product 


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disposition, as required by federal law, consist of the date received, date administered, quantity 
administered, and the participant number to whom the drug was administered.  
The Investigational Pharmacist will be responsible for maintaining accurate records of the 
shipment and dispensing of the investigational product. The pharmacy records must be available 
for inspection by the KEMRI SERU, Kenya PPB, the Kenya Ministry of Health, USAMRDC ORP, 
HRPO, the NIAID, OHRP, the US FDA, WRAIR, and other local or international regulatory 
entities, and is subject to inspection by a regulatory agency (e.g., FDA) at any time. An assigned 
Study Monitor will review the pharmacy records. 
3.4.1 FINAL DISPOSITION OF STUDY PRODUCTS 
All remaining unused study products at non-U.S. clinical research sites, which were supplied by 
the NIAID CRPMC, must be destroyed on site (as directed by the Sponsor) after the study is 
completed or terminated.  The procedures to be followed and relevant forms are in the Pharmacy 
Guidelines and Instructions Manual.  


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 PARTICIPANT ELIGIBILITY AND MANAGEMENT 
 
STUDY POPULATION 
126 Healthy adults aged between 18 and 40 years will be recruited from Kericho, Kenya. The site’s 
participant screening to enrollment ratio is anticipated at four (4) screened one (1) enrolled.  
Approximately 504 volunteers will be screened to enroll 126 study participants. 
 
ELIGIBILITY CRITERIA 
4.2.1 INCLUSION CRITERIA 
1. Healthy, male and female participant aged 18 to 40 years and available for 26 
months  
2. Must be at low risk for HIV infection per investigator assessment and using 
the study risk assessment tool.  
3. Must be able to understand and complete the informed consent process. 
4. Must be capable of reading English or Kiswahili.  
5. Must agree to a home visit.  
6. Willing to have photo or fingerprint taken for identification purposes. 
7. Must complete a Test of Understanding (TOU) before enrollment.  Must 
answer 9 out of 10 questions correctly, with a maximum of three attempts. 
8. Must be in good general health without a clinically significant medical history. 
9. HIV-uninfected per diagnostic algorithm within 45 days of enrollment. 
10. Laboratory values: 
• Hemoglobin: 
12.5-18.1 g/dL men 
11.0-16.1 g/dL women 
• White Cell Count: 
2.7-7.7 x 103 cells/μL men 
3.0-9.1 x 103 cells/μL women 
• Platelets: 
125-370 103 cells/μL men 
125-444 103 cells/μL women 
• ALT and AST: ≤1.25 institutional upper limit of the reference range 
Creatinine: ≤1.25 institutional upper limit of the reference range 
• Urinalysis: (dipstick) for blood and protein less than 1+ and negative glucose 


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Female-Specific Criteria: 
11. Negative urine pregnancy test for women at screening, the day of each 
vaccination, and before any invasive procedure. 
12. Already using and commits to continued use of an adequate birth control 
method for 45 days before to the first vaccine/placebo vaccination and for at 
least 90 days after the final vaccine/placebo vaccination.  Adequate birth 
control is defined as follows: Contraceptive medications delivered orally, 
intramuscularly, vaginally, or implanted, underneath the skin, surgical 
methods (hysterectomy or bilateral tubal ligation), condoms with spermicide, 
diaphragms, intrauterine device (IUD), vasectomy in a monogamous partner, 
or abstinence. 
4.2.2 EXCLUSION CRITERIA 
A history of:  
1. Three or more sexual partners in the previous 24 weeks 
2. Commercial sex work 
3. Non-adherence to condom use in the absence of a long-term monogamous 
relationship 
4. Intravenous drug use in the previous year. 
5. A sexually transmitted infection in the previous 24 weeks 
6. Is not a sexually active MSM or a transgender person in the past 6 months. 
7. Asplenia: any condition resulting in the absence of a functional spleen 
8. Bleeding disorder diagnosed by a medical doctor (e.g., factor deficiency, 
coagulopathy, or platelet disorder requiring special precautions) 
9. Breastfeeding or pregnant (positive pregnancy test) women or planning to 
become pregnant during the window between study enrollment and three 
months after the last vaccination visit. 
10. Any past, ongoing, or in remission history of treated or untreated autoimmune 
disease. 
11.  Has known active Hepatitis B virus infection (or positive HBsAg). 
12. Has known active Hepatitis C infection 
13. History of anaphylaxis or other serious adverse reaction to vaccines or allergies 
or reactions likely to be exacerbated by any component of the vaccine and 
placebo, including antibiotics or excipients 
14. Absolute Neutrophil Count (ANC): 
<1.0 x 103 cells/μL 
15. Participant has received any of the following substances: 


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• Chronic use of therapies that may modify immune response, such as intravenous 
(IV) immune globulin and systemic corticosteroids (in doses of >20 mg/day 
prednisone equivalent for periods exceeding 10 days) 
• The following exceptions are permitted and will not exclude study participation:  
o use of corticosteroid nasal spray for rhinitis,  
o topical corticosteroids for an acute uncomplicated dermatitis; or 
o A short course (10 days or less, or a single injection) of corticosteroid for a 
non-chronic condition (based on investigator clinical judgment) at least 2 
weeks before enrollment. 
16. Blood products within 120 days before HIV screening 
17. Immunoglobulins within 30 days before HIV screening 
18. Any experimental vaccine containing an adjuvant other than aluminum or an 
adjuvant not approved by the FDA or European Medicines Agency (EMA) as 
part of a licensed vaccine.   
19. CERVARIX vaccine against HPV (containing AS04) 
20. Receipt of any investigational HIV vaccine, investigational research agents or 
vaccine within 30 days before enrollment. 
21. Anti-tuberculosis prophylaxis or therapy during the past 90 days before 
enrollment 
22. Any psychiatric, social condition, occupational reason, or other responsibility 
that, in the judgment of the investigator, is a contraindication to protocol 
compliance or impairs a participant’s ability to give informed consent 
23. Major psychiatric illness and or substance abuse problems during the past 12 
months that, in the opinion of the investigator, would preclude participation 
24. History of atopy or significant skin conditions 
25. Study site employees who are involved in the protocol and or may have direct 
access to the study-related area 
Final evaluation of eligibility is based on the medical judgment of the investigator.  The PSRT will 
also remain available to PI for consultation if desired. 
 
LYMPH NODE BIOPSY ELIGIBILITY CRITERIA 
4.3.1.1 Lymph Node Biopsy Inclusion Criteria 
1. Body mass index (BMI) <35 
2. Platelets > 150,000  
3. International normalized ratio (INR) < 1.2 


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4. Verbal report of no NSAIDS/aspirin for 7 days prior 
5. Negative Pregnancy test for participants born female 
4.3.1.2 Lymph Node Biopsy Exclusion Criteria 
1. History of keloid formation 
2. History of an inguinal hernia, inguinal canal cryptorchidism, varicocele, hydrocele 
3. Local infections (or lymphadenitis) or rash in the groin, even if limited to the 
contralateral groin 
4. History of inguinal excisional lymph node biopsy 
 
PARTICIPANT MANAGEMENT 
4.4.1 PARTICIPANT RESPONSIBILITIES  
In addition to meeting the eligibility criteria listed above, participants will also be asked to agree 
to not participate in any other research study or donate blood during their participation in the RV 
460 study. 
4.4.2 WITHDRAWAL FROM THE STUDY, DISCONTINUATION OF STUDY PRODUCT, OR STUDY 
TERMINATION  
4.4.2.1 
Withdrawal 
• Repeated failure to comply with protocol requirements  
• Recommended withdrawal by the study investigator, e.g., because of worsening health 
status, intercurrent illness, or AEs interfering with study assessments as determined by the 
site investigator  
• Participant requests withdrawal    
Each participant has the right to withdraw from the study at any time for any reason without 
affecting the right to treatment.  The study staff should attempt to contact participants who did not 
return for scheduled visits or follow-up.  Although the participant is not obliged to give a reason 
for withdrawing prematurely, the investigator should make a reasonable effort to ascertain the 
reason(s) while fully respecting the participant’s rights. Participants who elect to not receive 
additional vaccinations may be asked to continue follow up assessment for safety until resolution 
in the case of an on-going AE.   
The study team will use several approaches that include at least three phone call attempts each to 
participant and to a confidant through contacts the participant would have provided and 
documented in the participant contact information form. If the participant is not located by phone 
call attempts, a home visit will be done to locate the participant. If after the home visit the 
participant cannot be contacted, they will be declared lost to follow-up. 


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For those participants who are unable to continue participation in the study, but who do not 
withdraw consent, an exit visit will be conducted. Any participant who withdraws consent will not 
have any further data collected after consent has been withdrawn.  
Participants may elect to withdraw consent for future use of their biological specimens or data at 
any time.  This will be recorded in the EDC and source and the data samples will be marked to not 
be used in the future. The data and specimens will be destroyed within one year of receiving 
notification from the protocol chair that all protocol testing is complete. Samples remaining in the 
KEMRI/USAMDR-A CRC repository will be destroyed by laboratory staff following approved 
laboratory procedures. 
See Appendix A: Schedule of Evaluations  
4.4.2.2 
Participant Replacement 
Participants who withdraw, are withdrawn from this study, or are lost to follow-up after signing 
the informed consent form (ICF) and administration of the study product will only be replaced if 
enrollment is still open.  If a participant withdraws from the study or discontinues vaccination 
before all slots have been filled, the vacated randomization slot will be filled with the next 
available participant.   
4.4.2.3 
Early Discontinuation of Vaccinations or Withdrawal of a Study Participant 
A participant may have vaccinations discontinued or will be taken out of the study entirely under 
the following circumstances:  
4.4.2.3.1 Immediate Early Discontinuation 
1. Upon learning of pregnancy 
2. Due to an SAE that is believed to be related to study vaccination, including 
a. Any Grade 3 systemic adverse reaction that is assessed as related to the study agent, 
b. Any Grade 4 adverse event assessed as related to the study agent, and 
3. Infection with HIV-1. 
4.4.3 MANAGEMENT OF MEDICAL CONDITIONS 
Participants will be offered pre-test counseling before HIV testing is done.  When giving HIV 
results to participants, post-test counseling will be done, and those who test positive will be 
referred to KCRH, or any other health facility of their choice, for HIV care and treatment.  The 
HIV pre and post-testing counselling will be provided by a psychological counsellor at the site, as 
well as by study clinicians/nurses trained in HIV counselling and testing. 
All individuals with clinical sexually transmitted infections (STIs) will be treated according to the 
Kenya Ministry of Health local standards of care. 
For all other medical illnesses and abnormal laboratory values, participants will consult study staff 
for treatment and or referral to the appropriate health facility during the study period. 


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4.4.4 MANAGEMENT OF PARTICIPANTS WHO BECOME PREGNANT 
Pregnant women are excluded from enrollment, however, if a participant becomes pregnant during 
the study, further vaccinations will be stopped, and she will be referred for maternal and child 
health services.  Participants will continue to be followed for the remainder of the study period for 
safety, and the study team will follow the course of the pregnancy until the outcome is documented.  
During subsequent study visits, blood draws will be conducted for safety evaluations only.  No 
optional collections or procedures will be performed. 
The Kericho site PI or designated associate investigator will be responsible for reporting any 
pregnancy to the PSRT and the study database.  The PSRT will review this information.  The site 
PI will forward notification as necessary to the WRAIR IRB and KEMRI SERU (Scientific and 
Ethics Review Unit). 
Pregnancy outcomes will be recorded via a standardized case report form.  Information 
documented on this form will include the date of last menstrual period, the date that the pregnancy 
was confirmed, any history of complications during prior pregnancies (such as congenital 
abnormalities or spontaneous abortions), and the outcome of the pregnancy including date of 
termination or delivery, any complications of pregnancy, and the status of the child.  A separate 
case report form will be completed for the delivered child to document date of delivery, gender, 
weight, the presence of any congenital abnormalities, American Pediatric Gross Assessment 
Record (APGAR) score, HIV status, and any other complication of delivery. 
4.4.5 MANAGEMENT OF PARTICIPANTS WHO BECOME INCARCERATED 
Participation of prisoners is not planned, and any participant will be suspended from study visits 
while incarcerated, except visits or telephone contact for ensuring their safety.  No study product 
will be administered to a participant who is incarcerated.  The IRB will be notified of the period 
of incarceration.  Data and samples that were collected before the period of incarceration may still 
be stored and used for analyses.  After release from incarceration, either the participant may return 
to participation in study visits according to the SOE or study participation may be terminated at 
the discretion of the PI. 
Any participant who is incarcerated will be re-consented before rejoining the study. 
4.4.6 MANAGEMENT OF PARTICIPANTS WITH VACCINE-INDUCED SEROPOSITIVITY (VISP) OR 
SEROREACTIVITY (VISR) 
Participants who receive study vaccine (not placebo) may subsequently receive a false positive on 
an HIV antibody test.  Participants are asked to contact the PI or study staff if at any time during 
or after study participation if an HIV test is requested outside of the study.  If a participant has an 
issue due to a false-positive HIV test result from receiving the vaccination, the PI will provide an 
explanatory letter, and the study will provide re-testing.   
4.4.7 TRANSPORTATION 
The study team anticipates that nearly all participants or their confidants will have a phone.  For 
those participants who are unable to be contacted by phone, community mobilizers will contact 
them with a home visit. In order to adequately locate participant’s home, all participants will be 
dropped home after the first vaccination visit and the exact location of their homes documented in 


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the locator form. We will use alternative contacts to trace them if they are not home.  Study 
participants will use public transport to and from the study site.  Public transportation is good and 
reliable at recruitment catchment area.  Transportation will not be provided by the study team 
except in the event of extenuating circumstances when a participant does not have adequate means 
of transportation for clinic visits.  If the participant did not use the site’s transport, they would also 
receive reimbursements for transportation, taking into consideration the average cost of travel to 
the clinic. 
4.4.8 UNBLINDING PROCEDURES 
Once all study visits have completed, the Kericho site investigators will contact study participants 
by phone or through a home visit to invite them to come back to the clinic to find out whether they 
received the study product or placebo.  When the participant returns to the clinic for unblinding, 
they will be given a letter that indicates their study arm.  


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 STUDY PROCEDURES 
 
RECRUITMENT 
Potential subjects will be made aware of the need for study participants through planned 
community sessions, church gatherings, public meetings, government administrative meetings 
(chief’s baraza’s) or because of previous trial participation. Participants will be invited to attend a 
general information session at the KEMRI/USAMRD-A Clinical Research Center. After the 
information session, individuals that indicate interest in the study will be invited and scheduled to 
attend a briefing session (using the WARIR IRB approved slides) at their convenience.  The 
Principal Investigator (PI) or designee will conduct briefing sessions at regular intervals 
throughout the recruitment phase.  After the briefing, the potential participants with have the 
opportunity for questions.  All participants interested in this study will subsequently be 
administered informed consent individually.  
 
CONSENT PROCEDURES AND SCREENING 
All participants that present for screening will be documented in a screening log.  
Potential subjects must be literate to participate in the study and the consent forms will be offered 
in English and Kiswahili.  The PI or their designee will review the consent form in detail with 
potential participants and answer any questions.  Written informed consent will be obtained from 
each participant before any study procedures are performed.  All informed consent forms will be 
administered individually, in a private setting, with respect for confidentiality.  Participants will 
be given ample time and opportunity to inquire about the details of the study, discuss the study 
with family members or friends, and ask any questions before signing the informed consent forms.  
A copy of the signed informed consent form will be given to the participant along with a copy of 
the participant event schedule.  The consenting process will be documented in the case report forms 
(CRFs).After providing signed informed consent, the participant will complete a TOU.  
Participants can take the TOU three times but must have a passing score of 90% or greater by the 
third attempt to participate in the study.  If after three attempts to pass the TOU, and the participant 
is unable to do so, the participant will become ineligible for study participation. 
Participants who have passed the TOU and have given written informed consent will then undergo 
a review of complete medical history including medications, physical examination, and screening 
laboratory assessments to determine eligibility for trial participation.   
Counseling on the potential risks of becoming pregnant during this trial will be provided.  Pre-
HIV test counseling and post-HIV test counseling as well as HIV prevention guidance will be 
provided during the screening process. 
Study participants might be scheduled for a second screening visit to evaluate abnormal, not 
medically significant, findings (including laboratory tests).  If the participant presents with an 
abnormality or illness that is determined to likely be related to a transient illness, they could also 
be invited back for reassessment.  


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Upon screening or rescreening, the investigator may discover an illness or condition that requires 
treatment.  The site will provide primary care and treatment as per Kenyan National guidelines 
and refer these participants to an appropriate healthcare facility for further evaluation and 
treatment. 
Participants that elect to have cervicovaginal secretion collection will undergo a routine PAP smear 
for assessment of inflammation or other abnormality including cellular changes.  Abnormal results 
will be discussed with the participant and treatment or referral for care will be provided. Abnormal 
PAP results are exclusionary for the optional cervicovaginal secretion collection only. 
 
ENROLLMENT AND RANDOMIZATION 
There will be 18 participants per group (15 vaccine recipients and 3 placebo recipients).  
Investigators will be blinded to vaccine versus placebo within each group but not across groups.  
Participants will be block randomized.   Group 1 (with a prime of Env-C Plasmid DNA IM alone 
at weeks 0, 4, 12) will be fully enrolled first.  After the 18 participants in Group 1 are enrolled, the 
remaining groups, 2-7, will begin enrolling participants.  Once 24 participants in Groups 2-7 have 
been enrolled (four from each group) and received their first vaccinations, enrollment and 
vaccinations in Groups 2-7 will be paused for the time it takes the PSRT to review (typically 3 to 
14 days) blinded safety data from these 24 participants covering the period immediately after their 
first vaccination through Day 7.  If it is determined to be necessary by the PSRT, the MHRP SMC 
will be consulted to review unblinded data to provide a recommendation on continuing enrollment. 
When safety has been confirmed with PSRT review, the remaining 14 participants in each of 
Groups 2-7 will be enrolled, and vaccinations will continue until the first 24 participants in Groups 
2-7 (four per group) have received their first boost dose (at 20 weeks—to create a time gap between 
boost vaccinations of the first cohort and the remaining study participants).   
A second scheduled pause  (this pauses boost vaccinations only; prime vaccinations can continue) 
will occur for Groups 2-7 after the same set of participants reviewed during the first scheduled 
pause (the first 24 participants (four per group) from Groups 2-7) has received its first boost (Group 
1 can continue receiving vaccinations).  This pause will review blinded safety data from these 24 
participants, covering the period from the first boost through Day 7 after that boost.  At both 
scheduled pauses, the PSRT will consult the SMC regarding the pause if either of the following 
conditions are met: 1) one (or more) participants experience an SAE that is related to a study agent, 
or 2) two (or more) participants experience grade 3 or 4 AEs of the same type (e.g. elevated ALT) 
related to a study agent.  Boost vaccinations for Groups 2-7 will resume once safety data from the 
booster sentinel cohort have been reviewed by the PSRT and they have concluded it is safe to 
proceed. 
 
VACCINATION  
The site for injection cleaned with an alcohol wipe before the injection. The vaccines will be given 
by intramuscular (IM) injection into the deltoid muscle, excluding the dmLT adjuvant which is 
given by TCI. Alternating deltoids will be used for subsequent immunizations. A study vaccination 
outside of a participant’s vaccination window may occur at the discretion of the PSRT. 


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STUDY VISITS 
Participants will have up to 26 clinic visits.   The active study phase will last a total of 105 
weeks, which will include the time of the first screening visit through the final clinic study visit. 
In addition, participants will be contacted once per week for 3 weeks (3 phone contacts) 
following the 105 week active study phase. At these contacts, staff will collect the information 
listed below. 
• Confirmation of vital status; if deceased, attempt to learn cause and date of death; 
• If participant is alive, record the participant’s responses to questions regarding any 
occurrence of the following events since the last study contact: 
• Life-threatening adverse experiences; 
• Persistent or significant disability/incapacity; 
• Hospitalizations and reasons; 
• New diagnosis of HIV infection; and 
• Pregnancies and outcomes, including congenital anomalies/birth defects 
All such events will be recorded, and adverse events other than HIV infection will be assessed 
for relationship to study product(s). Clinic visits will only be required if HIV confirmatory 
testing is necessary; however, a clinic visit may be arranged for other reasons. 
Evaluation of the safety of the study vaccines is outlined in the schedule of evaluations (SOE) 
and will include laboratory studies, medical history, physical assessment by clinicians, and 
participant self-assessment recorded on a 7-day diary card.  Additional study visits may be 
required if, in the investigator’s opinion, any lab value warrants repeating.  The first vaccination 
visit could take up to 6 hours, but the other vaccination visits take about 4 hours each. Most other 
follow-up clinic visits will usually take about 2 hours.   
Total blood volume drawn from each participant will not exceed the US Department of Defense 
(DoD), American Association of Blood Banks (AABB) and FDA guidelines of 450 mL in an eight-
week period.  If a participant is anemic, each visit’s blood volume will be reviewed, and the blood 
drawn for research may be reduced or not drawn at all, depending on the severity of anemia. 
 
 
  


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Table 4: Visit Procedures  
Clinic visit activities 
 
Screening Visit 
• Study briefing and collection of contact information 
• Informed consents  
• Test of understanding 
• Review medical history including medications 
• Vital signs (blood pressure, pulse, respiratory rate, and oral temperature)  
• Complete physical exam including height and weight 
• CBC, creatinine, ALT, and AST 
• HIV risk counseling  
• HIV test with counseling before and after 
• Hepatitis B and C 
• Syphilis test 
• Pregnancy counseling 
• Urine pregnancy test for women 
• Urinalysis (dipstick) for blood, protein, and glucose  
 
Optional 
• Pap smear for women who agree to cervicovaginal secretion collection 
Vaccination Visits 
• Targeted physical exam and review of current medication  
• Vital signs (blood pressure, pulse, respiratory rate, and oral temperature)  
• Review eligibility  
• HIV risk counseling  
• Blood draw for safety*, research and HIV tests 
• Pregnancy counseling 
• Urine pregnancy test for women 
• Enrollment and randomize*  
• Administer vaccination or placebo 
• Post-injection observation for 30-60 minutes  
• Adverse event documentation 
• Provide a diary card and instruction 
 
Optional  
• Mucosal secretion collection*  


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Phone/Clinic Follow Up Visits after Each Vaccination and as Needed 
• Assessment of wellbeing 
• Measure vital signs (blood pressure, pulse, respiratory rate, and oral temperature) if the 
participant comes to the clinic 
• Review of symptoms  
• Adverse event documentation 
Telephone follow-up will be the default method for this visit.  Home visits will be done for 
those participants who will not be reachable by phone. 
Follow Up Visits to Include Final Visit 
• Targeted physical exam and review of concomitant medication 
• Measure vital signs (blood pressure, pulse, respiratory rate, and oral temperature)  
• Body weight, if clinically indicated 
• HIV risk counseling  
• Pregnancy counseling 
• Urine pregnancy test for women if mucosal secretion collection or lymph node biopsy* 
• Review of diary card*   
• Adverse event documentation 
• Blood draw for safety, research, and HIV tests* 
 
Optional  
• Mucosal secretion collection*  
• Lymph node biopsy and biopsy site assessment*  
 
* See Appendix A: Schedule of Evaluations  
 
OPTIONAL PROCEDURES 
5.6.1 MUCOSAL COLLECTIONS 
Participants will have the option of participating in separately consented mucosal collections.  
These collections will be conducted at the Kericho site at baseline and subsequent intervals per the 
SOE.  Every effort will be made to have the procedures begin early, and in the event that this is 
not achieved, the procedures will be split and done over two consecutive days, within the study 
visit window. 
5.6.1.1 
Female Participants  
Female participants may choose to undergo in cervicovaginal secretion and or rectal sponge 
secretion collections. Rectal secretions will be collected by rectal sponges by use of a rectal 
speculum and 2-4 sponges are inserted into the rectum mucosa for at least 4 minutes. The collected 
sponges will be placed in a sterile conical tube and shipped to the lab for processing. Consenting 
women will be instructed on how to use a Softcup device to collect cervicovaginal secretions.  The 
cup will remain in place for 4-12 hours.  Women that consent for cervicovaginal secretion 
collection will undergo a PAP smear test at screening.  A urine pregnancy test will be done prior 
to each collection. Pregnant women and those with a history of toxic shock syndrome will be 
excluded.  Date of last menstrual period will be recorded at each collection visit. The collection 
will not take place if the woman is menstruating or has symptoms of active inflammation or 


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infection of the vagina or cervix.  Rectal sponge secretions will also be collected however will be 
deferred if there are signs or symptoms of perianal inflammation.  Participants will be asked to 
refrain from penetrative sex up to 72 hours prior to Softcup or sponge placement.   
5.6.1.2 
Male Participants  
Male participants may participate in semen collection and or rectal sponge secretion collections. 
Consenting men will be asked to ejaculate into a sterile container for semen collection.  Rectal 
secretions will be collected by rectal sponges by use of a rectal speculum and 2-4 sponges are 
inserted into the rectum mucosa for at least 4 minutes. The collected sponges will be placed in a 
sterile conical tube and shipped to the lab for processing. Rectal sponge secretions will also be 
collected at this visit if the participant agrees.  Semen and rectal sponge collections will be deferred 
from men if there are signs or symptoms of urethral or perianal inflammation, respectively.  
Participants may participate in semen collection and or rectal sponge secretion collections. 
5.6.2 LYMPH NODE BIOPSIES 
Excisional lymph node biopsies have been performed (for reasons other than sentinel node staging 
for cancer) by research sites around the world including MHRP sites in Kenya, Uganda, Tanzania, 
Thailand in HIV-infected and uninfected study participants, without any post-operative severe 
sequelae.  Moreover, a recent article describing a meeting of experts discussed the importance of 
evaluating germinal center responses following immunization to predict broadly neutralizing 
antibody potency and breadth.  A review of existing data showed that risks associated with 
excisional biopsies are low and with few complications [94]. 
Willing study participants will have the option of participating in a separately consented procedure 
of excision of intact inguinal lymph nodes.  Inguinal lymph node excision will be offered at week 
14 and week 58 and will be performed by a qualified doctor trained to perform superficial lymph 
node excision.  The procedure will be performed under local anesthesia and last approximately 30-
40 minutes.  Anesthetics, antiseptics, and antibiotics are per surgeon’s SOP and will be modified 
if the participant reports an allergy or sensitivity.  Participants will then be asked to rest under 
observation for another 2-3 hours.  Post-procedure, participants will return to the clinic in about 1 
week for assessment of the biopsy site.   
Coagulation testing will be done approximately 1 week before each biopsy and urine pregnancy 
testing will be done just prior to each biopsy. 
Participants will be asked for their consent for photography if the clinician wishes to document an 
unusual or unexpected finding. Pictures may also be taken of the biopsy site immediately after the 
procedure and again 6 months later in order to provide an objective reference for biopsy site 
healing (i.e. for participant safety) and for possible use as participant educational material (for 
other participants who undergo the same procedure).  
Assessment of the biopsy site includes: 
• Evaluation for infection 
• Seroma 
• Cellulitis 


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• Lymphedema 
• Pain 
• Bleeding 
• Hematoma 
• Erythema 
• Scarring 
• Adhesive tape reaction 
• Numbness or altered sensation of the area. 
 
INFORMATION SHEET ON COVID-19 
In light of the circulating severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and 
the associated coronavirus disease (COVID-19) pandemic, the clinic will provide to the 
participant at time of consent an information sheet regarding proposed modifications put in place 
to safeguard the health and well-being of participants. The modifications provide flexibility for 
conducting study visits and procedures when needed to monitor participant safety. These 
modifications are expected to be time-limited in relation to the COVID-19 pandemic. In 
consultation with the Sponsor and MHRP, the study team will determine when, in the future, the 
guidance is no longer applicable. WRAIR and SERU will be notified when such a determination 
is made. 


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 LABORATORY ASSESSMENTS  
 
BLOOD SAMPLES 
After collection, all specimens will be transported to the site laboratory according to a standard 
operating procedure (SOP).  Samples will be packaged in appropriate isothermal containers for 
transportation.  On arrival at the laboratory, all specimens will be logged into a sample tracking 
database before distribution to the different assay benches for processing. 
Blood processing is performed using Good Clinical Laboratory Practices (GCLP), with personal 
protective equipment, including lab coats, gloves, and laminar flow hoods.  All specimens will be 
labeled with barcode indicating participant identification numbers (PID), sample type, date and 
study visit number and will be indexed and cross-referenced in a specimen-tracking database. The 
processing lab staff will only know the PID to ensure confidentiality. 
Blood collected for plasma or serum specimens will be centrifuged, aliquoted, and stored at –70oC 
or colder.   PBMCs will be isolated, cryopreserved and stored in the vapor phase of a liquid 
nitrogen freezer.  Mucosal Specimens will be processed according to standard laboratory operating 
procedures and stored -70℃ or colder freezer.  All specimens will be labeled with barcode 
indicating: PID, sample type, date and study visit number and will be indexed and cross-referenced 
in a specimen-tracking database.  These procedures are detailed in the laboratory MOP.  
6.1.1.1 Laboratory tests to assess safety 
Clinical laboratory testing will take place in the CAP-certified laboratory and includes pregnancy 
testing, complete blood count, chemistry (Creatinine, ALT, AST) and HIV testing.  HIV testing 
will be performed according to the approved laboratory algorithm including 4th generation 
immunoassay and nucleic acid testing when indicated.  Safety labs may be repeated if clinically 
indicated. 
6.1.2 IMMUNOGENICITY TESTS 
Cryopreserved samples will be shipped to laboratories at MHRP/WRAIR, Armed Forces Research 
Institute of Medical Sciences (AFRIMS) or other laboratories listed to perform the assays listed 
below.  Additional assays/analytes may be added that fall into the categories described in the 
schedule of events.   
6.1.2.1 
HIV-1-specific binding antibody assays 
Binding antibody assays will be performed to detect serum, plasma, or mucosal secretion binding 
antibodies to a broad array of HIV-1 antigens.  Serum and plasma will be also tested for their 
ability to block HIV-1 binding to the α4β7 receptor and other possible HIV-1 co-receptors.  In 
addition, antibody isotype, subclass, FC gamma, complement usage, and other antibody profiling 
tools may be utilized in parallel with antigen specificity.    Monoclonal antibodies may also be 
isolated from selected vaccine recipients. 


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6.1.2.2 
Functional antibody assays 
Antibody-dependent Cell-Mediated Cytotoxicity (ADCC) Assay and Antibody-dependent Cell-
Mediated Viral Inhibition (ADCVI) Assays: ADCC assays will be performed at visits specified in 
the SOE using rapid fluorometric ADCC assay.  Other functional assays may include but are not 
limited to Antibody-dependent Cell-Mediated Phagocytosis (ADCP) and Antibody-dependent 
Complement (ADC) activation assays.   
6.1.2.3 
Neutralizing antibody assays 
Neutralization assays will be performed similarly to other HIV vaccine trials using cell line-based 
and PBMC assays with a panel of viruses from different HIV subtypes, including A, B, C, D, and 
other circulating recombinant forms (CRFs) such as AE and AG.  
6.1.2.4 
Cellular immune assays 
Cryopreserved PBMC and lymph nodes will be stimulated with HIV-1-specific antigens and tested 
using standard (but not limited to) cellular immune assays which may include but are not limited 
to Intracellular Cytokine Staining, ELISPOT, Lymphoproliferation assays, B-cell analysis, T-
follicular helper cell, and innate immune cell analysis 
6.1.3 OTHER ASSAYS 
• Gene expression/transcriptomic analysis using current technologies. 
• Genetic analysis including but not limited to Human Leukocyte Antigen (HLA) subtyping. 
• Soluble factor/cytokine analysis:  Levels of soluble inflammatory markers will be 
evaluated representing different biological pathways such as general inflammation, tumor 
necrosis factor-α (TNF-α) signaling, IFN-γ signaling, and lymphocyte activation.  
Additional markers may be included.  
• Sequencing of HIV-1 RNA to characterize viral features and assess the effect of the vaccine 
if a volunteer becomes infected with HIV-1 during the study. 
 
FUTURE USE AND STORAGE OF BIOLOGICAL SAMPLES 
Each study participant will be asked to voluntarily consent to their blood samples to be stored for 
other research studies that may be done after this study is complete.  Future testing may involve 
genetic tests.  In case the participant is unwilling to have their biological samples stored for future 
use, they can consent to participate in this study only, without having their blood samples stored 
for future testing.  In this case, their blood samples will be destroyed within one year of receiving 
notification from the protocol chair that all protocol testing is complete. Samples remaining in the 
KEMRI/USAMDR-A CRC repository will be destroyed by laboratory staff following approved 
laboratory procedures. 
All samples for which consent has been obtained and for which additional material is available 
after study specified testing is complete will be stored for future testing at the KEMRI/USAMRD-
A CRC Laboratory in Kericho.  However, KEMRI SERU and WRAIR IRB approval will be 
sought before any such samples are used for analysis not specified in the protocol or a protocol 
amendment approved by the IRB.  All samples belong to the site from which they were obtained 
and MHRP. 


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During the study, blood samples will be tested soon after collection.  The remaining samples will 
then be stored at the KEMRI/USAMRD-A CRC lab.  For specialized tests that are not available at 
this site some of the blood samples will be shipped to the United States for HIV immune response 
testing as well as genetic testing.  Shipment of these samples will be done only after the approval 
of the KEMRI SERU. 


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 DATA MANAGEMENT AND ANALYSIS 
 
STUDY DOCUMENTATION, STORAGE, AND DATA COLLECTION 
Signed Informed Consent Forms (ICFs) and study documents are kept in a room that is double 
locked with limited access.  The investigators and staff are responsible for ensuring maintenance 
of a comprehensive centralized filing system of all study-related (essential) documentation, 
suitable for inspection at any time by the following organizations will be granted direct access to 
the participant’s original medical records: KEMRI SERU, Kenya PPB, the Kenya Ministry of 
Health, NIAID, US FDA, WRAIR,  USAMRDC, ORP, HRPO, and the people who work for these 
organizations, and other local, US or international regulatory agencies.  Participants information 
may also be reviewed or inspected for verification of clinical trial procedures and or data.  
Inspections will be conducted without violating the confidentiality of the participant, to the extent 
permitted by the applicable laws and regulations and that, by signing a written informed consent 
form, the participant is authorizing such access.  
Data will be collected using source documents and or Case Report Forms (CRFs). Direct entry 
using tablets or computers is possible depending on the current site capability.  Data will be 
uploaded daily to the central DCAC database.  Access to the data collection software is limited to 
PI approved staff and requires unique usernames and passwords.  Data are housed in a secure 
database maintained by the DCAC, MHRP in accordance with Good Clinical Practices (GCP).  
Study data are referenced only by the study-specific identification code. The study records will be 
stored at the KEMRI/USAMRD-A triple-locked filing room for the period when the study is 
active, and thereafter transferred to the site’s archive for long term storage. All participants 
consented will be assigned a 7-digit Participant Identification (PID). Participant IDs will be 
assigned sequentially, for example 460-0001. 
 
ANALYSIS 
7.2.1 POWER AND SAMPLE SIZE 
The safety, reactogenicity, and tolerability of the vaccine regimens are the primary endpoints for 
this study.  Below in Table 6, the estimated probability of a participant having at least one of these 
events (in percent), along with the associated exact Clopper-Pearson 95% confidence interval, is 
given for various numbers of observed events that correspond to approximate event rates within 
study groups of possible interest.  Note that some event rates cannot be exactly observed within a 
given group, depending on the sample size (e.g. 10% of 15 participants is 1.5 participants, which 
is rounded to 2 in the table below). 


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Table 5: Estimated probability (in percent) of a participant having at least one AE, along with the associated exact Clopper-
Pearson 95% CI, given varying sample sizes and numbers of participants with at least one observed AE 
Group 
n 
Approximate AE Rate1 
0% 
10% 
20% 
50% 
Corresp
onding 
# AEs2 
Estimated 
Probability 
(95% CI) 
Corresp
onding 
# AEs2 
Estimated 
Probability 
(95% CI) 
Corresp
onding 
# AEs2 
Estimated 
Probability 
(95% CI) 
Corresp
onding 
# AEs2 
Estimated 
Probability 
(95% CI) 
Each Individual Group 
15 
0 
0 (0, 21.8) 
2 
13.3 (1.7, 
40.5) 
3 
20 (4.3, 
48.1) 
8 
53.3 (26.6, 
78.7) 
Placebo 
21 
0 
0 (0, 16.1) 
2 
9.5 (1.2, 
30.4) 
4 
19 (5.4, 
41.9) 
11 
52.4 (29.8, 
74.3) 
Any DNA Prime with HIV Env 
gp145 C.6980 /Rehydragel 
Boosts 
105 
0 
0 (0, 3.5) 
11 
10.5 (5.3, 
18.0) 
21 
20 (12.8, 
28.9) 
53 
50.5 (40.5, 
60.4) 
DNA alone (1+2), DNA+TCI 
(3+4), DNA/ALF43 (5+6) 
30 
0 
0 (0, 11.6) 
3 
10 (2.1, 
26.5) 
6 
20 (7.7, 
38.6) 
15 
50 (31.3, 
68.7) 
HIV Env gp145 C.6980 
/Rehydragel boost (1+3+5), HIV 
Env gp145 C.6980 
/Rehydragel/ALF43 boost 
(2+4+6) 
45 
0 
0 (0, 7.9) 
5 
11.1 (3.7, 
24.1) 
9 
20 (9.6, 
34.6) 
23 
51.1 (35.8, 
66.3) 
Any ALF43 
75 
0 
0 (0, 4.8) 
8 
10.7 (4.7, 
20.0) 
15 
20 (11.6, 
30.8) 
38 
50.7 (38.9, 
62.4) 
1 The approximate proportion of participants in a group reporting at least one event of interest 
2 The number of participants with observed event(s) needed to most closely correspond to the given approximate event rate, with the 
given sample size 
For illustration, if 2 individuals among the 15 participants in an individual vaccine group experienced at least one event, the estimated 
event probability would be 13.3%, with an associated exact 95% CI of (1.7%, 40.5%).  Eleven individuals reporting at least one event 
among all active participants (n=105) would lead to a similar estimated event probability of 10.5%, but with a narrower exact 95% CI 
(5.3%, 18%). 


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The table below gives the probability of observing at least one or more than one event in a group 
of interest, given underlying per-subject probabilities of at least one event. 
Table 6: Probability of observing at least one or at least two safety events in a given group, 
given varying underlying per-participant probabilities of experiencing at least one event 
Underlying Probability of At Least One Event 
1% 
10% 
20% 
Group 
n 
>0 
>1 
>0 
>1 
>0 
>1 
Each Individual Vaccine Group 
15 
14.0% 
1.0% 
79.4% 
45.1% 
96.5% 
83.3% 
Placebo 
21 
19.0% 
1.9% 
89.1% 
63.5% 
>99% 
94.2% 
Any Env-C Plasmid DNA Prime with 
HIV Env gp145 C.6980 /Rehydragel 
Boosts 
105 65.2% 
28.3% 
>99% 
>99% 
>99% 
>99% 
Env-C Plasmid DNA alone (1+2), 
Env-C Plasmid DNA+TCI (3+4), Env-
C Plasmid DNA/ALF43 (5+6) 
30 
26.0% 
3.6% 
95.8% 
81.6% 
>99% 
>99% 
HIV Env gp145 C.6980 /Rehydragel 
boost (1+3+5), HIV Env gp145 
C.6980 /Rehydragel/ALF43 boost 
(2+4+6) 
45 
36.4% 
7.5% 
>99% 
94.8% 
>99% 
>99% 
Any ALF43 
75 
52.9% 
17.3% 
>99% 
>99% 
>99% 
>99% 
 
7.2.2 PRIMARY ANALYSIS 
The primary endpoints of this Phase 1 study are related to the safety, reactogenicity and tolerability 
of the Env-C Plasmid DNA vaccine regimens.  These will be monitored by PSRT and SMC as 
appropriate, and SAE), AEs and PIMMC will be recorded until the end of the trial. 
SAEs, AEs, AESIs, reactogenicity, and tolerability will be tabulated by study group and 
combinations of interest.  Exact 95% Clopper-Pearson confidence intervals will be calculated for 
each set of events, and the maximum severity and relatedness will be reported for each participant.  
While the study was not designed with the purpose of detecting safety differences, comparisons 
between regimens or between groups of interest and the placebo controls may be made.  These 
comparisons would be made at a two-sided α=0.05 level, using the normal approximation to the 
binomial distribution (z-test) as mentioned in the previous section, or an alternate testing procedure 
as appropriate (e.g. Fisher’s Exact test for smaller samples).  No adjustments for multiple 
comparisons will be made. 
7.2.3 SECONDARY ANALYSIS 
The secondary endpoints of this study involve the immune response to the vaccination regimens 
in either the systemic and mucosal compartments.  The laboratory assays used to measure these 
various immune response endpoints typically result in continuous measurements for each 
participant. 


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For each continuous immune response variable of interest, means, medians, ranges and 95% Wald 
confidence intervals will be computed.  Proportions and exact 95% Clopper-Pearson confidence 
intervals will be computed for any categorical variables. 
Comparisons of these endpoints between study groups may be made using non-parametric Mann-
Whitney U tests, and once again, no adjustments for multiple comparisons will be made due to the 
hypothesis- generating nature of the study.  The groups will be the same as used for the safety 
comparison but also may include other groups.  For any categorical secondary endpoints, Fisher’s 
Exact tests or asymptotic tests assuming normality will be used as appropriate. 
7.2.4 EXPLORATORY AND SUBGROUP ANALYSES 
Exploratory and subgroup analyses involve additional immune response endpoints as well as DNA 
microarrays.  These will be analyzed similarly to the secondary endpoints.  For any genetic 
analyses, control of the false discovery rate (FDR) at the 0.1 level will be made via p-value 
adjustment. 
After the assays for the secondary and exploratory endpoints are finalized and before the final 
analyses have begun, a statistical analysis plan (SAP) will be created to elucidate upon these details 
and make any changes as necessary. 


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 SAFETY AND REPORTING 
 
ASSESSING AND RECORDING SAFETY PARAMETERS 
8.1.1 REACTOGENICITY  
8.1.1.1 
Diary Card (7-Day Solicited Reactogenicity)  
Reactogenicity events are AEs that are common and known to occur following administration of 
this type of study vaccine. A diary card will be used to aid in the collection of potential reactions. 
Temperature and solicited local and systemic symptoms will be recorded in the clinic before 
vaccination and 30-60 minutes post-injection, at home about 6 hours after vaccination, and then 
daily by the participant for 7 days. Solicited symptoms that persist after the end of day 7 will be 
considered an AE or SAE, will be documented, and followed through resolution. 
At each vaccination visit, participants will be given a new diary card, a thermometer and a ruler.  
The diary card will be used as a memory aid, on which the participant will record oral temperature, 
local and systemic symptoms, and concomitant medications daily for 7 days, beginning with the 
day of vaccination.  Participants will be trained to complete the diary card, how to use the 
thermometer, and how to measure injection site swelling and redness using the ruler after each 
vaccination.  Completion of the diary card training will be noted in source documents.  The diary 
card is not a source document; the information gained from the review of the diary card and the 
interview with participants will be documented using a combination of progress notes and CRFs 
maintained in the participants research chart.   
The solicited signs and symptoms on the diary card are:  
Local 
• Pain/tenderness 
• Itching 
• Warmth 
• Redness/erythema measurement of largest dimension 
• Swelling/induration measurement of largest dimension 
Systemic 
• Fever 
• Myalgia 
• Arthralgia 
• Headache 
• Fatigue 
• Chills 
• Rash  
• Nausea 


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• Dizziness 
Where multiple assessments are taken on the same day, participants will be requested to record the 
day’s highest measured temperature and measurement of largest dimension for redness and 
swelling.  
Follow-up on participant well-being will be performed by telephone (preferred method) or clinic 
visit on the day following vaccination (and up to 48 hrs. later).  Diary cards will be reviewed with 
the clinician on day 7 ± 2 following each vaccination.  If upon reviewing the diary card, the 
clinician finds that local or systemic information (except swelling, redness, temperature 
measurements) is missing from the diary card, or the diary card is lost, the participant will be asked 
to provide the missing information to the best of their recollection.  The missing data, such as 
temperature measurements will be indicated as missing in the database and a lost diary card will 
not result in a protocol deviation. 
8.1.2 MANAGEMENT OF VACCINATION REACTIONS 
Participants will be observed in the KEMRI/USAMRD-A CRC by study staff for 30 to 60 minutes 
after vaccination.  On vaccination days, there will be at a minimum one physician investigator 
available for assessment of any reaction. 
In the event of a severe allergic reaction, the CRC is staffed with trained medical personnel and 
stocked with appropriate medical emergency equipment to provide acute care for conditions such 
as anaphylaxis.  If needed, participants will be transferred to the Unilever Hospital for further 
assessment and care. 
8.1.3 ADVERSE EVENTS (AES) 
ICH E6 defines an AE as any untoward medical occurrence in a patient or clinical investigation 
participant administered a pharmaceutical product regardless of its causal relationship to the study 
treatment.  FDA defines an AE as any untoward medical occurrence associated with the use of a 
drug in humans, whether considered drug related. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of medicinal (investigational) 
product.  The occurrence of an AE may come to the attention of study personnel during study visits 
and interviews of a study recipient presenting for medical care, or upon review by a study monitor.  
All AEs, including solicited local and systemic reactions, will be documented and included as 
source for the eCRF and maintained in the participant’s research chart.  Information to be collected 
for AEs includes:  
• Event description 
• Date of onset 
• Assessment of severity 
• Relationship to study product and  


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• Alternate etiology (assessed only by those with the training and authority to make a 
diagnosis and listed on the form FDA 1572 as an investigator) 
• Date of resolution 
• Seriousness and  
• Outcome 
AEs occurring during the trial collection and reporting period will be documented appropriately 
regardless of relationship.  AEs will be followed through resolution. Any medical condition that 
is present at the time that the participant is screened will be considered as baseline and not reported 
as an AE.  However, if the severity of any pre-existing medical condition increases, it should be 
recorded as an AE. 
An SAE: An adverse event or suspected adverse reaction is considered "serious" if, in the view of 
either the investigator or sponsor, it results in any of the following outcomes: death, a life-
threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions, or a congenital anomaly/birth defect.  Important medical events that may not result in 
death, be life-threatening or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the participant and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition.  Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an emergency room 
or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse (21 CFR 312.32).  
“Life-threatening” refers to an adverse event that at occurrence represents an immediate risk of 
death to the participant.  An event that may cause death if it occurs in a more severe form is not 
considered life-threatening.  Similarly, hospital admission for an elective procedure is not 
considered an SAE.  The clinician will ask each participant about other interim adverse experiences 
and recorded this information in the source documents.  Study staff will enter AE or SAE 
information into the study database within three business days of the participant visit.  After study 
day 28 after the last vaccination, only SAEs and new chronic medical conditions that require 
ongoing medical management will be entered into the database, through the last study visit.  All 
other adverse events will be recorded on source documents only.  The PI or designee will assess 
the relationship of the study product to the events. 
If an event meets both the criteria of a study endpoint and an adverse event, the event will be 
reported either as a study endpoint or as an adverse event (not both). 
8.1.4 SERIOUS ADVERSE EVENTS (SAES)  
An adverse event or suspected unexpected adverse reaction (SUSAR) is considered “serious” if, 
in the view of either the investigator or sponsor, it results in any of the following outcomes:   
• Results in death,  
• Is life-threatening,  
• Requires inpatient hospitalization or prolongation of existing hospitalization,  


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• Results in persistent or significant disability/incapacity,  
• Is a congenital anomaly/birth defect 
• Is an important medical event that may not be immediately life-threatening or result in 
death or hospitalization but may jeopardize the patient or may require intervention to 
prevent one of the other outcomes listed in the definition above.  
Important medical events that may not result in death, be life-threatening, or require 
hospitalizations may be considered serious when, based upon appropriate medical judgment they 
may jeopardize the participant and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition.  Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
Life-threatening adverse event: An AE is considered “life-threatening” if, in the view of either 
the site principal investigator or sponsor, its occurrence places the participant at immediate risk of 
death.  It does not include an AE that, had it occurred in a more severe form, might have caused 
death. 
SAEs will be assessed for severity and relationship to study product and alternate etiology (if not 
related to study product) by the PI or AI listed on the Form FDA 1572 and followed through 
resolution.  
8.1.5 POTENTIALLY IMMUNE-MEDIATED MEDICAL CONDITIONS (PIMMCS) 
PIMMCs constitute a group of AEs that includes diseases which are clearly autoimmune in 
etiology and other inflammatory and/or neurologic disorders which may or may not have 
autoimmune etiologies.  
8.1.6 MEDICALLY ATTENDED ADVERSE EVENTS 
The FDA requests that clinical trials of preventive vaccines with adjuvants such as ALF43 and 
dmLT provide for collection and analysis of data relating to medically attended adverse events 
(MAAEs) among subjects in all treatment groups through 12 months or longer following the last 
study vaccination, due to the theoretical potential for induction of autoimmune or auto-
inflammatory diseases. 
MAAEs are defined as AEs with medically attended visits including hospital, emergency room, 
urgent care clinic, or other visits to or from medical personnel for any reason. Adverse events (e.g., 
abnormal vitals) identified at a routine study visit will not be considered MAAEs.  
8.1.7 ADVERSE EVENT ASSESSMENT 
All AEs (laboratory and clinical symptoms) will be graded for severity and assessed for 
relationship to study product using the DAIDS Table for Grading the Severity of Adult and 
Pediatric Adverse Events (DAIDS AE Grading Table), Version 2.1 dated July 2017 that is found 
on the website https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables. 
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The start and stop date of each reported AE will be recorded on the appropriate data collection 
form and eCRF. Changes in the severity of an AE will be documented to allow an assessment of 
the duration of the event at each level of intensity. Adverse events not identified in the grading 
table, follow the guidelines provided at the beginning of the table.  
8.1.8 ADVERSE EVENT DOCUMENTATION 
The clinician will ask each participant about other interim adverse experiences and record this 
information in the source documents.  Study staff will enter data into the study database within 
three business days of participant visits.  28 days after the last vaccination, only SAEs and new 
chronic medical conditions that require ongoing medical management will be entered into the 
database, through the last study visit.  All other adverse events will be recorded on source 
documents only.  The PI or designee will assess the relationship of the study product to the events.  
Participants will be asked for their consent for photography if the clinician wishes to document an 
unusual or unexpected finding. 
8.1.8.1 
Severity vs. Seriousness of Adverse Events  
The term “severity” describes the intensity of a specific event. The severity of a specific event is 
graded, i.e., mild (Grade 1), moderate (Grade 2), severe (Grade 3), potentially life-threatening 
(Grade 4), or death (Grade 5) using the DAIDS AE Grading Table Version 2.1. The severity of an 
AE does not determine whether an event meets the definition of seriousness, which is based on 
participant/event outcome or action criteria associated with events that pose a threat to a 
participant’s life or functioning (ICH E2A). 
8.1.8.2 
Relationship to Study Product 
The site investigator is responsible for assessing the relationship between the AE and the study 
agents. Site investigators must determine whether there is a reasonable possibility that the study 
agents caused or contributed to a and AE or SAE. The relationship assessment, based on clinical 
judgment, often relies on the following:  
• A temporal relationship between the event and administration of the study agents,  
• A plausible biological mechanism for the agent to cause the AE,  
• Another possible etiology for the AE,  
• Previous reports of similar AEs associated with the study agent or other agents in the same 
class, and  
• Recurrence of the AE after re-challenge or resolution after de-challenge, if applicable.  
The terms used to assess the relationship of an event to study agent are:  
Related – There is a reasonable possibility that the AE may be related to the study agents.  
Not Related – There is not a reasonable possibility that the AE is related to the study agents.  
When a SAE is assessed as “not related” to study agents, an alternative etiology, diagnosis, or 
explanation for the SAE should be provided. If new information becomes available, the 
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When the study agent is a fixed dose combination agent, an assessment of attribution will be made 
for each component and the combination agent. 
8.1.8.3 
Expectedness  
Expected AEs are AEs that have been previously observed with use of the study agent(s) and are 
listed in the package insert or Investigator’s Brochure. Expectedness is not based on what might 
be anticipated from the pharmacological properties of the study agent.  
Unexpected AEs are AEs for which the nature or severity (intensity) is not consistent with the 
applicable agent information (Investigator’s Brochure, package insert, or summary of agent 
characteristics).  
8.1.8.4 
Type and Duration of Follow-up of Participants after Adverse Events 
AEs will be assessed and followed from initial recognition of the AE through end of the protocol 
defined follow-up period.  SAEs will be followed up through resolution even if duration of follow-
up goes beyond the protocol-defined the follow-up period.  Resolution of an AE is defined as the 
return to pre-treatment status or stabilization of the condition with the expectation that it will 
remain chronic. 
 
EXPEDITED ADVERSE EVENT (EAE) REPORTING  
8.2.1 EAE REPORTING  
Requirements, definitions and methods for expedited reporting of adverse events are outlined in 
Version 2.0 of the DAIDS EAE Manual, which is included in the manual of operations (MOP) and 
available on the DAIDS RSC website at https://rsc.niaid.nih.gov/clinical-research-sites/manual-
expedited-reporting-adverse-events-daids. 
The DAIDS Adverse Experience Reporting System (DAERS), an internet-based reporting system, 
must be used for EAE reporting to DAIDS. In the event of system outages or technical difficulties, 
EAEs may be submitted using the DAIDS EAE Form. This form is available on the DAIDS RSC 
website at https://rsc.niaid.nih.gov/clinical-research-sites/paper-eae-reporting. 
For 
questions 
about 
DAERS, please 
contact 
NIAID 
CRMS 
Support 
at 
CRMSSupport@niaid.nih.gov. Please note that site queries may also be sent from within the 
DAERS application itself. 
For questions about expedited reporting, please contact the DAIDS RSC Safety Office at 
DAIDSRSCSafetyOffice@tech-res.com. 
All serious adverse events (SAEs) that are considered related or possibly related, and all deaths, 
will be promptly (within 48 hours) reported to the WRAIR IRB. The Principal Investigator will 
then submit written reports within 10 working days to the WRAIR IRB.  Follow up reports will be 
submitted as additional information becomes available. A summary of the non-serious adverse 
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included in the continuing review report to the WRAIR IRB.  The WRAIR HSPB will report SAEs 
to the USAMRDC ORP HRPO as per UWZ-C-636.” 
8.2.1.1 
EAE Reporting Requirements for the Study 
The SAE or SUSAR Reporting Category, as defined in Version 2.0 of the DAIDS EAE Manual, 
will be used for this study. 
The study products for which expedited reporting are required are:  
• HIV-1gp120 (93MW965.26) DNA (Env-C Plasmid DNA) 
• HIV Env gp145 C.6980 protein 
• dmLT 
• ALF43  
• Rehydragel® 
In addition to the SAE or SUSAR Reporting Category identified above, other adverse events that 
must be reported in an expedited manner are: 
Potentially Immune-Mediated Medical Conditions (PIMMCs) 
8.2.1.2 
Grading Severity of EAEs 
DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 
2.1 (DAIDS AE Grading Table) is used that is available on the DAIDS RSC website at 
https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverse-event-grading-tables.  
8.2.1.3 
EAE Reporting Period 
The EAE reporting period for this study is 108 weeks after study agent administration until study 
completion or discontinuation of the participant from study activity for any reason as per the 
DAIDS EAE Manual. 
After the protocol-defined EAE reporting period, unless otherwise noted, only SUSARs as defined 
in Version 2.0 of the DAIDS EAE Manual will be reported to DAIDS if the study staff become 
aware of the events on a passive basis (from publicly available information). 
All SAEs and SUSARS will be reported by the site PI or designee to the: DAIDS RSC Safety 
Office 
(DAIDSRSCSafetyOffice@tech-res.com) 
and 
MHRP 
COO 
(reportable_events@hivresearch.org).  
The DAIDS Medical Officer, who determines if an IND Safety Report will be sent to the FDA, 
performs the final attribution of the SAE.  If the SAE is assessed as related, the RSC must submit 
an IND Safety Reports to the FDA no later than seven (death or life-threatening) or 15 calendar 
days following receipt of the information from the site. 


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8.2.1.4 
Submission of Updated Information on Expedited Adverse Events  
Sites must follow each AE until the AE is resolved or stable. For each AE reported to DAIDS, 
sites are required to submit an updated report to DAIDS as soon as significant additional 
information becomes available. The following are examples that must be submitted:  
• An updated report documenting the stable or resolved outcome of the AE, unless the initial 
report included a final outcome, 
• Any change in the assessment of the severity grade of the AE or the relationship between 
the AE and the study agent, or 
• Additional significant information on a previously reported AE (e.g., cause of death, results 
of re-challenge with the study agents). 
8.2.1.5 
Reporting Recurrent Adverse Events on an Expedited Basis  
For an event previously reported to the DAIDS Safety Office, if the AE fully resolved but then 
reoccurs with an outcome meeting expedited reporting criteria, the AE must be reported as a new 
initial report to the DAIDS Safety Office. 
 
HALTING OR PAUSING RULES 
8.3.1 NOTIFICATION OF AES MEETING STUDY PAUSE CRITERIA  
The PI notifies the PSRT, which includes the DAIDS MO, study chair, site PI, DoD research 
monitor or their designees within a few hours after the site is aware of the AE.  The PSRT will 
convene within one business day to review these adverse events and determine disposition 
(including whether the SMC needs to review the event). 
If a decision to resume study enrollment and study treatment administration is made, the PSRT 
and or SMC will record its judgment in a memorandum to the study file and notify DAIDS.  The 
MHRP Clinical Operations Office (COO) will then forward the memorandum to the principal 
investigators and notify WRAIR IRB.  As needed, the appropriate regulatory authorities will be 
informed in writing of the decision to resume or discontinue study activities.  Kericho site is 
responsible for notifying KEMRI SERU and WRAIR IRB according to local standards and 
regulations.  The sponsor (DAIDS) is responsible for notifying the FDA.  
For SAEs, sites must also follow the DAIDS EAE Manual and submit the SAE to DAIDS 
Regulatory Support Center (RSC) Safety Office as soon as possible, but no later than 3 reporting 
days (as defined in the DAIDS EAE Manual v2.0), after the site’s recognition that the event fulfills 
the criteria for SAE reporting.   
For IND Safety Reports submitted to the FDA and received from DAIDS, the MHRP COO will 
complete the necessary reporting to WRAIR IRB, including telephone contact and a written report 
generated within 24 hours of the initial safety report.  WRAIR HSPB will forward to the 
USAMRDC, ORP, HRPO. 
If the trial is placed on an unscheduled safety pause, all enrollment and study agent 
administrations will be suspended until further notice. For the two scheduled safety pauses, 


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enrollments and vaccinations for Group 1 do not need to be paused; only Groups 2-7 would be 
affected.  For any study pause or re-initiation after a pause, the study staff will contact the 
participants to inform them.  If the study is on pause for vaccinations, safety blood work is 
continued per protocol.  Vaccinations are resumed post-pause but those who have missed vaccine 
windows would resume based on consultation with the PSRT on a case-by-case basis based on 
the number of vaccinations missed, length of pause, etc.  
The PSRT will closely monitor and analyze study data as they become available and will make 
determinations regarding the presence, severity, and seriousness of adverse events.  The 
administration of study injections and new enrollments will be paused, and DAIDS (the IND 
Sponsor) will be promptly notified according to the following criteria:  
• One (or more) participant experiences a SAE that is assessed as related to study agent, or 
• Two (or more) participants experience the same Grade 3 or 4 AE assessed as related to a 
study agent.  
8.3.2 PLAN FOR REVIEW OF PAUSES AND RESUMING RULES  
The study injections and enrollments would resume only if the review of the adverse events that 
caused the pause resulted in a recommendation to permit further study injections and study 
enrollments.  The reviews to make this decision will occur as follows: 
Pauses for SAEs: The PSRT may consult with the SMC to conduct the review and make the 
decision to resume, amend, or close the study for any SAEs that meet the criteria for pausing the 
study.  The FDA will be notified of any SAE pause review. 
Pauses for two or more Grade 3 or 4 AEs (e.g., two grade 4 ALT): The PSRT will conduct the 
review and make the decision to consult the SMC, resume, amend or close the study for the Grade 
3 or 4 events that meet the criteria for pausing the study.  As part of the SMC review, the reviewers 
will also advise on whether the study needs to be paused again for any subsequent Grade 3 or 4 
event of the same type.  
When indicated, safety data reports and changes in study status will be submitted to the IRB. 
 
SAFETY OVERSIGHT  
8.4.1 SAFETY MONITORING COMMITTEE (SMC) 
Oversight for several MHRP research protocols will be provided by an SMC, which consists of 
independent clinicians, scientists, statisticians and/or ethicists who collectively have experience in 
vaccines or therapeutics as well as the conduct of clinical trials.   
The MHRP SMC will be consulted by the PSRT to review unblinded data to provide a 
recommendation on continuing enrollment if there are any questions regarding safety.  The SMC 
may again be consulted to review data from three weeks after the 21st participant has received 
their first “boost” vaccination at week 20.  


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Subsequently, the SMC will convene every six months to review the completeness of the study 
data collected, the adherence to the protocol, and the PI/core team summary.   
The SMC will also meet as needed to deliberate upon the disposition of study pauses, and or to 
provide other recommendations regarding the safe conduct of the study as requested by the PSRT, 
and or DAIDS.  The SMC Executive Secretary will provide the Protocol Chair and DAIDS 
Medical Officer with SMC recommendations.  MHRP COO to WRAIR HSPB will submit SMC 
Reports, and the RV460 PI will submit the reports to KEMRI SERU and the Kenya Expert 
Committee on Clinical Trials (ECCT), of the Pharmacy and Poisons Board (PPB). 
8.4.2 DEPARTMENT OF DEFENSE (DOD) RESEARCH MONITOR 
The DoD Research Monitor may perform oversight functions (e.g. observe recruitment, enrollment 
procedures, and the consent process for participants; oversee study interventions and interactions; 
review monitoring plans and UPIRTSO reports; oversee data collection, and analysis) and report 
their observations and findings to the IRB.  The DoD research monitor may discuss the research 
protocol with the investigators, interview human participants, and consult with others outside of 
the study about the research.  The research monitor shall have authority to stop a research protocol 
in progress, remove individual participants from a research protocol, and take whatever steps are 
necessary to protect the safety and well-being of participants until the IRB can assess the monitor’s 
report.  Research Monitors have the responsibility to report within 48 hours their observations and 
findings to the IRB.  The DoD Research Monitor is required to review all unanticipated problems 
involving risks to participants or others, SAE reports, and all participant deaths.  The DoD 
Research Monitor at a minimum must comment on the outcomes of the event or problem and in 
case of a serious adverse event or death, comment on the relationship to participation in the study.  
They must also indicate whether he/she concurs with the details of the report provided by the PI. 
The DoD Research Monitor should review all initial reports for SAEs, unanticipated problems 
involving risks to participants or others, and all participant deaths promptly and provide their 
independent report.  The Research Monitor will provide an unbiased written report of all 
unanticipated problems involving risks to participants or others, and related SAEs and deaths, 
within 48 hours to the WRAIR IRB by phone 301-319-9940, or by email (usarmy.detrick.medcom-
wrair.mbx.hspb@mail.mil).  All Research Monitor reports for unrelated SAEs and deaths should 
be kept with the corresponding SAE reports at the study site. A written Research Monitor report 
will be submitted within 10 working days to the WRAIR IRB. 
The WRAIR HSPB will submit copies of these reports to the USAMRDC, ORP, HRPO as per 
SOP UWZ-C-636. 


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 HUMAN SUBJECTS PROTECTION 
 
INFORMED CONSENT  
The legal age at which individuals can provide their own consent to participate in research is 18 
years.  Consent forms will be available in English and Kiswahili. 
There are four consent forms to be used for this study: 
1. Main Informed Consent Form  
2. Optional Procedures Consent Form  
3. Withdrawal of Consent Form (as needed)  
4. Photography Consent Form (as needed) 
Information will be given in both oral and written form whenever possible and deemed appropriate 
by the IRB.  A clinical investigator or designee will describe the study to potential participants.  
The investigator or designee (e.g., study coordinator) shall give the participant ample opportunity 
to inquire about details of the study, discuss with other people and ask any questions before dating 
and signing the consent forms.  Participant information and consent form language will be at a 
reading level to be fully comprehensible to the prospective participants. 
The participant and the study staff conducting the informed consent explanation will sign and date 
the consent form.  The participant’s signature confirms that she or he has understood the 
information.  Each participant’s consent form will be kept in his or her study file and a copy will 
be given to the participant to take home on the same day.  Any amendments to the protocol 
resulting in a change in study procedures will necessitate that the study participants be informed, 
and additional informed consent obtained if necessary.  
In accordance with 32 CFR 219, 45 CFR 46 and 21 CFR 50 and Good Clinical Practice, the 
participant may terminate participation in the study at any time for any reason without penalty.  
Additionally, if the participant is unable or unwilling to adhere to the protocol design, the 
investigator may terminate their participation.  Under such circumstances, data and sample already 
collected may be stored and available for analysis.  In addition, if the administration of research 
product has occurred, following for safety will be attempted. 
Informed consent is a process that is initiated prior to an individual agreeing to participate in a trial 
and continues throughout the individual’s trial participation.  Before any study procedures are 
performed, informed consent will be obtained and documented.  An investigator or designee will 
give a concise and focused face-to-face presentation describing key protocol information to 
potential participants.  The information conveyed will include the explanation that the trial 
involves research and identifying which aspects of the trial that are experimental, the probability 
for random assignment to treatment groups, any expected benefits, all possible risks and the 
expected duration of the participant’s participation in the trial.  The presentation will be organized 


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and presented in lay terminology and language that facilitates understanding why one might or 
might not want to participate. 
Participants will receive an explanation as to whether any compensation and any medical 
treatments are available if injury occurs, and, if so, what they consist of, or where further 
information may be obtained. They will be informed of whom to contact (e.g., the investigator) 
for answers to any questions relating to the research project. Participants will be informed in a 
timely manner if information becomes available that may be relevant to their willingness to 
continue participation in the trial. 
Information presented to potential participants will also include the foreseeable circumstances and 
or reasons under which the participant’s participation in the trial may be terminated. The 
participants will be informed that participation is voluntary and that they are free to withdraw from 
the study for any reason at any time without penalty or loss of benefits to which the participant is 
otherwise entitled.   
Participants will be informed that, as part of their responsibilities for ensuring the protection of 
research participant, the following will be granted direct access to the participant’s original 
medical records: KEMRI SERU, Kenya PPB, USAMRDC, ORP, HRPO, the NIAID, the US FDA, 
the Kenya Ministry of Health, WRAIR, the people who work for these organizations, and other 
local, US or international regulatory agencies.  Participants information may also be reviewed or 
inspected for verification of clinical trial procedures and or data.  Inspections will be conducted 
without violating the confidentiality of the participant, to the extent permitted by the applicable 
laws and regulations and that, by signing a written informed consent form, the participant is 
authorizing such access. 
Participants will be informed that records containing identifying information will be kept 
confidential, and, to the extent permitted by the applicable laws and or regulations, will not be 
made publicly available and, if the results of the trial are published, the participant’s identity will 
remain confidential. Participants will be informed whether private information collected from this 
research and or specimens will be used for additional research, even if identifiers are removed.   
Participants will be allowed enough time to read and review the ICFs to consider participation in 
this research trial and can discuss this trial with their family or friends or think about it prior to 
agreeing to participate. The informed consent forms will be administered individually with strict 
respect for confidentiality. 
 
POTENTIAL RISKS AND BENEFITS 
9.2.1 POTENTIAL RISKS 
9.2.1.1 
Risks of Study Agent Administration and Their Mitigation 
Participants may exhibit general signs and symptoms associated with a vaccine or placebo 
injection including fever, chills, rash, aches and pains, nausea, headache, dizziness, and fatigue.  
These side effects will be monitored but are generally short-term and do not require treatment.  


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Participants may have an allergic reaction to the vaccination.  An allergic reaction may manifest 
as a rash, hives or even difficulty breathing.  Severe reactions are rare.  To minimize this risk, 
those with a history of anaphylaxis or other serious adverse reaction to vaccines or allergies or 
reactions likely to be exacerbated by any component of the vaccine or placebo, including 
antibiotics, will not be allowed to participate in this study.  Study staff will observe participants 
for 30 to 60 minutes after vaccination.  On vaccination days, there will be at a minimum one 
physician investigator available for assessment of any reaction.  In the event of a severe allergic 
reaction, the CRC is staffed with trained medical personnel and stocked with appropriate medical 
emergency equipment to provide acute care for conditions such as anaphylaxis.  If needed, 
participants will be transferred to the Unilever Hospital for further management. 
TCI is a needle-free skin patch procedure which itself (without antigen) is safe and well tolerated 
in humans [53], [95].  In general, TCI-vaccinated participants may exhibit a local vaccine site 
reaction that was generally of mild-to-moderate severity.  The majority (68.3%) of vaccine site 
reactions were characterized as erythematous and papular, while a smaller proportion of vaccine 
site reactions were characterized as either erythematous (13.9%) or papular (8.9%) only.  Erythema 
and papules were both present in participants after receipt of the first vaccine dose (both at 43.5%); 
however, their frequency appeared to increase after receipt of the second (erythema: 76.7%; 
papules: 74.4%) and third (erythema: 75.6%; papules: 63.4%) vaccinations (not statistically 
significant).  Local site reactions also consisted of pigmentation changes, the majority (47/53; 
88.7%) of which occurred in individuals with a preceding papular rash.  Both hyper and 
hypopigmentation may occur at the site and persist for some time.  It is thought these reactions are 
dependent on the antigen tested by the TCI method. 
TCI with LT has been safe with usually only Grade 1 side effects: pruritus, mild redness or rash, 
and hyperpigmentation at the site of patch application in different incidence and duration 
depending upon the site preparation method and patch used for the trial.  These side effects were 
most likely also influenced by the activation of adenylate cyclase from the A subunit of the LT, 
which should be absent in the double mutant LT to be evaluated in this study [94].  Overall, when 
dmLT has been tested with TCI, it has been safe and well tolerated in most of human clinical trials 
(See IB). 
9.2.1.2 
Vaccine-Induced Seropositivity (VISP) or Seroreactivity (VISR) 
Participants who receive study vaccine (not placebo) may subsequently receive a false positive on 
an HIV antibody test.  Participants are asked to contact the PI or study staff if at any time during 
or after study participation if an HIV test is requested outside of the study.  If a participant has an 
issue due to a false-positive HIV test result from receiving the vaccination, the PI will provide an 
explanatory letter and the study will provide re-testing.  A positive or indeterminate test may have 
negative employment and social impact; as a result, a letter of participation will be provided on 
request. 
Participants will be discouraged from donating blood during study participation because of the 
potential false-positive HIV antibody test result.  If these test results should occur, Western blot 
analysis will be augmented with PCR or other required testing to either exclude or confirm HIV 


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infection.  Blood donation options for those participants who wish to resume blood donation will 
be explained at the final study follow-up visit. 
9.2.1.3 
Social Harms 
There is a risk of social harms other than described above regarding VISP.  The study staff 
encourage open communication with participants and are aware if the potential for harms including 
but not limited to embarrassment, privacy loss, judgement by family, friends, and employers. The 
researchers take these risks seriously, and, depending on the situation, the clinic staff will provide 
appropriate assistance if preventive measures have failed.  
9.2.1.4 
Unknown Risks 
There may be other serious risks that are not known with the study vaccines. 
Participants may believe that this vaccine provides HIV protection, and therefore practice riskier 
behavior.  They will receive extensive counseling throughout the study to address this potential 
problem.  It is not known if the vaccines increase or decrease the chance of becoming HIV infected 
when exposed or if becoming HIV infected the person’s disease course progresses faster to AIDS. 
9.2.1.5 
Unknown Risks related to Immune-Based Diseases 
Experimental vaccines may hypothetically unmask or worsen an immune-based disease or 
syndrome e.g., Guillain-Barre or true autoimmune arthritis (such that objective physical signs last 
longer than six months).  A variety of HIV-1 Env antigens very similar to those in this study have 
been evaluated extensively in humans and have not caused autoimmune diseases.  However, 
whenever new adjuvants are tested in humans, study participant will be closely monitored for 
immune-based diseases.  In a prior study evaluating the earlier generation of ALF43, L(MPLA), 
two cases of multiple sclerosis (MS) were reported; but they were diagnosed several years after 
the last vaccination, and one of the cases received an additional three unrelated experimental 
vaccines before the diagnosis, so that attribution of the event to the first experimental vaccine 
would have been impossible.   
See IB Clinical Section on ALF for details and Appendix O: List of PIMMCs.  
9.2.1.6 
Study Risks Related to Pregnancy and Their Mitigation 
The effect of these study agents on a fetus or nursing baby is unknown so the following precautions 
will be taken: 
• Women who are pregnant or nursing will be excluded from the study, 
• Female participants of childbearing potential will be required to agree to use at least one 
method of effective birth control for sexual intercourse beginning 45 days before the first 
vaccination and continuing through 90 days after the last vaccine/placebo visit.  
Contraceptive medications delivered orally, intramuscularly, vaginally, or implanted, 
underneath the skin, surgical methods (hysterectomy or bilateral tubal ligation), condoms 
with spermicide, diaphragms, IUD, vasectomy in a monogamous partner, or abstinence, 
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• Women must also have a negative pregnancy test before collection of cervicovaginal 
secretion samples, before lymph node biopsy and before receiving study agent 
administration.  
• Women who become pregnant during the study will be referred for standard care treatment, 
and they will be followed up for safety reasons until the baby is born. 
9.2.1.7 
Risks of Phlebotomy 
Venipuncture may cause pain, bruising, and infrequently, presyncope.  Local infection at the 
phlebotomy site is also a risk of phlebotomy.  Rarely, it may cause infection at the phlebotomy 
site. Minor infections will be treated in the study clinic or will be referred to Kericho County 
Referral Hospital for further care and management, based on severity and clinical judgement. 
9.2.1.8 
Risks Related to Mucosal Secretion Collection 
Mucosal secretion samples collected in the clinic (rectal sponges, semen, and cervicovaginal cups) 
will be obtained noninvasively.  Semen will be self-collected and for the collection of 
cervicovaginal secretions, women may elect to insert and remove cervical cups themselves, as 
well.  Inserting an instrument or collection device into the anus or the vagina may cause discomfort 
and slight irritation.  There is no evidence of rectal sponge or cervical cup sampling contributing 
to the risk of HIV or other sexually transmitted infection.  For these non-invasive mucosal 
collections, men and women will be asked to refrain from receptive anal or vaginal, intercourse, 
douching, or inserting any product into the rectum or vagina for 3 days prior to the mucosal 
collection.  Men will be asked not to masturbate nor ejaculate three days prior to semen collection. 
9.2.1.9 
Risks Related to Lymph Node Biopsy 
Excisional inguinal lymph node biopsy will be performed under local anesthesia by a surgeon 
trained in superficial lymph node excision.  As with all surgical procedures, there is a risk of 
scarring, bruising or bleeding at the surgical site; these risks are minimized by the small nature of 
the incision (approximately 1-2 centimeters) and by prior clinical and laboratory evaluation to 
determine any bleeding risks.  Participants may experience some discomfort following the 
procedure despite the use of local anesthesia; for participants who complain of any subsequent 
discomfort, additional analgesia (such as paracetamol, diclofenac or ibuprofen) will be made 
available by the study site.  There is a possibility of seroma formation at the biopsy site, which 
may require subsequent drainage or further management, or sensory nerve injury during the 
procedure, which could result in a temporary or permanent local reduction in feeling.  Surgical site 
infection is a possible complication of any procedure involving an incision however, the risk is 
low [23].  Finally, there is the unlikely possibility that the procedure will be unsuccessful, and no 
lymph node will be recovered. 
9.2.1.10 
Risks from Human Leukocyte (HLA) testing 
Blood samples donated for HLA testing is used only to provide study investigators information 
about the immune system.  The results will be coded to protect participant identity.  The test results 
will NOT be provided to or shared with participants because they have not been validated for 
clinical management.  


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9.2.1.11 
Risks to Researchers 
Risks to researchers and their work include direct exposure to blood borne pathogens, in particular 
to HIV.  To mitigate these risks, staff members handling samples are trained on the safe use and 
handling of blood products utilizing universal precautions.  The study personnel are provided with 
and trained on the use of personal protective equipment (PPE) and on the containment of 
biohazards.  Trained staff will perform study procedures. 
In case of an accidental needle-prick, the staff has access to Post-Exposure Prophylaxis (PEP) 
services, and there is an SOP on the use of PEP at the site. 
9.2.2 POTENTIAL BENEFITS 
Although study participants may benefit from clinical testing and physical examination, they may 
receive no direct benefit from participation.          
 
COMMUNITY ADVISORY BOARD (CAB) 
The Kericho CAB serves as a link between the research team and the community.  The CAB will 
give feedback to the research team on issues about the study that might be of concern to the 
volunteers or the community at large.  One of our CAB members is a lawyer who will be able to 
address and guide us on any legal issues that may arise or be of concern during the conduct of 
research studies at this site. 
The CAB will be briefed about the study before community engagement commences. The briefing 
will be done by at least the PI/designated AI, study coordinator and the community liaison officer. 
The CAB will thereafter be involved on a need basis with a feedback meeting to be done at the 
end of participant follow-up. 
 
MANAGEMENT OF VULNERABLE POPULATIONS 
If the status of an enrolled participant changes during their participation in the study and or in that 
the participant’s ability to exercise free choice could be limited in some way, the participant is 
recognized as a vulnerable participant.  A vulnerable participant is any individual whose 
willingness to participate in a clinical trial may be unduly influenced by the expectation, whether 
justified or not, of benefits associated with participation; or of a retaliatory response from senior 
members of a hierarchy in case of refusal to participate. 
The participant that is likely to be vulnerable to coercion or undue influence, might include 
individuals such as minors, pregnant women, prisoners, soldiers, handicapped, or mentally 
incompetent persons.  
If a change in the status of a participant already enrolled in the study should occur, it is the 
responsibility of the investigators to assure that appropriate safeguards are in place to protect the 
rights, safety, and welfare of all study participants.  The principal investigator should promptly 
notify KEMRI SERU and WRAIR IRB.  The IRBs must decide what types of special protections 
are required and provide direction to the investigator. 


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9.4.1 PARTICIPATION OF CHILDREN 
Children are not eligible to participate in this clinical trial, because it does not meet the guidelines 
for inclusion of children in research.  These guidelines (45 CFR 46, Subpart D, 401-409) state the 
Department of Health and Human Services protections for children who participate in research.  
Generally, healthy children can be studied when the research is considered “not greater than 
minimal risk.”  Children can be involved in research with greater than minimal risk only when it 
presents the prospect of direct benefit to the individual child or is likely to yield generalizable 
knowledge about the child's disorder or condition. 
9.4.2 PARTICIPATION OF PRISONERS 
Participation of prisoners is not planned, and any volunteer will be suspended from study visits 
while incarcerated.  The WRAIR IRB will be notified of the period of incarceration.   
9.4.3 ILLITERATE PARTICIPANTS  
Illiterate persons are not eligible to participate in this study.  
 
FUTURE USE AND STORAGE OF BIOLOGICAL SAMPLES 
Each participant will be asked to voluntarily consent to their blood samples to be stored for other 
research studies that may be done after this study is complete.  Future testing may involve genetic 
tests.  In case the participant is unwilling to have their biological samples stored for future use, 
they can consent to participate in this study only, without having their blood samples stored for 
future testing. In this case, their blood samples will be destroyed within one year of receiving 
notification from the protocol chair that all protocol testing is complete. Samples remaining in the 
KEMRI/USAMRD-A CRC repository will be destroyed by laboratory staff following approved 
laboratory procedures. 
All samples for which consent has been obtained and for which additional material is available 
after study specified testing is complete will be stored for future testing at the KEMRI/USAMRD-
A CRC Laboratory in Kericho.  However, KEMRI SERU and WRAIR IRB approval will be 
sought before any such samples are used for analysis not specified in the protocol or a protocol 
amendment approved by the IRB.  All samples belong to the site from which they were obtained 
and MHRP. 
During the study, blood samples for safety testing will be tested as soon as possible and within the 
allowable sample stability timeframe for each test.  For specialized tests that are not available at 
this site, some of the blood samples will be shipped to the United States or Thailand for HIV 
immune response testing as well as genetic testing.  These shipments will occur in batch, when 
sufficient participants have reached appropriate timepoints in the schedule of events.  The 
remaining samples will then be stored at the KEMRI/USAMRD-A CRC lab.  Shipment of these 
samples will be done only after the approval of the KEMRI SERU. 


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RISKS FROM HUMAN LEUKOCYTE (HLA) AND OTHER GENETIC TESTING 
Blood samples donated for HLA testing are used only to provide study investigators information 
about the immune system.  The results will be coded to protect participant identity.  The test results 
will not be provided to or shared with participants because they have not been validated for clinical 
management.  
 
PARTICIPANT CONFIDENTIALITY 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and 
the sponsor and their agents. This confidentiality includes documentation, investigation data, 
participant’s clinical information, and all other information generated during participation in the 
study. No information concerning the study, or the data generated from the study will be released 
to any unauthorized third party without prior written approval of the DAIDS and the participant. 
Subject confidentiality will be maintained when study results are published or discussed in 
conferences.  The study monitors, or other authorized representatives of the sponsor or 
governmental regulatory agencies may inspect all documents and records required to be 
maintained by the investigator, including but not limited to, medical records (office, clinic, or 
hospital) and pharmacy records for the participants in this study. The clinical study site will permit 
access to such records. 
All records will be kept locked and all computer entry and networking programs will be carried 
out with coded numbers only and with password protected systems. All non-clinical specimens, 
evaluation forms, reports, and other records that leave the site will be identified only by a coded 
number. 
 
COSTS, REIMBURSEMENT, AND RESEARCH RELATED INJURIES 
9.8.1 POLICY REGARDING RESEARCH-RELATED INJURIES 
The US DoD is funding this protocol.  As stated in the protocol and consent form, participants 
who experience illness or injury arising from participation in the study will receive medical care 
for such illness or injury with costs for such care provided by a limited set-aside fund and a clinical 
trials medical insurance policy that will be obtained by the study funder.  While we anticipate the 
combination of the set-aside fund and the insurance policy is more than enough to pay for the 
research related injury medical care cost associated with this study, there is a limit to the amount 
of coverage available.  If the limit is exceeded, the study participant may have to pay non-covered 
costs.  Other than medical care, and other payments as stated in the consent form, there is no other 
compensation available from this research study. 
9.8.2 REIMBURSEMENT 
Participants will be reimbursed with Kenya shillings (KSH) 1000 for their time and any 
inconvenience during each scheduled study visit.  Reimbursement amounts are as follows: 
Study visits  


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(in person or by phone):   
1000 Ksh 
Unscheduled visits:    
Up to 500 Ksh, at the discretion of the study investigator 
Mucosal collection:    
1000 Ksh per each collection 
Lymph node biopsy:   
5000 Ksh 
Transportation:  
 
Up to 3000 Ksh, at the discretion of the study investigator 


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 INSTITUTIONAL REVIEW BOARDS AND REGULATORY 
REQUIREMENTS 
 INSTITUTIONAL REVIEW BOARDS 
Kenya Medical Research Institute SERU 
PO Box 54840-00200  
Nairobi, Kenya  
FWA#00002066  
 
Walter Reed Army Institute of Research IRB 
US Army Garrison-Forest Glen  
503 Robert Grant Avenue  
Silver Spring, MD 20910  
FWA #00000373  
The investigator will submit applicable information to the WRAIR IRB and KEMRI SERU for the 
review, to conduct the review in accordance with 45 CFR 46, ICH E6 GCP, and as applicable, 21 
CFR 56 (Institutional Review Boards) and 21 CFR 50 (Protection of Human Participants), DoD 
regulation 32 CFR 219, and other federal, state, and local regulations.  
The IRB must be registered with OHRP as applicable to the research.  DAIDS must receive the 
documentation that verifies IRB-approval for this protocol, associated informed consent 
documents, and upon request any recruitment material and handouts or surveys intended for the 
participants, prior to the recruitment and enrollment of participants. 
Any amendments to the protocol or consent materials will be approved by the IRB before they are 
implemented.  IRB review and approval will occur at least annually throughout the enrollment and 
follow-up of participants and may cease if annual review is no longer required by applicable 
regulations and the IRB.  The investigator will notify the IRB of deviations from the protocol and 
reportable SAEs, as applicable to the IRB policy. 
In addition, the protocol and associated documents will undergo review and approval by both the 
KEMRI SERU, WRAIR IRB and the USAMRDC, ORP, HRPO. 
10.1.1 REPORTING REQUIREMENTS TO THE KEMRI SERU 
The Kericho site PI will be responsible for providing all Safety Reports and reporting all SAEs, 
and study pauses, social harms, major deviations to KEMRI SERU promptly according to the 
institution’s guidelines.  “When reporting to KEMRI SERU, the PI will follow the reporting 
requirements of the WRAIR IRB as noted below in Sections 10.2 – 10.6.” 
10.1.2 ADDITIONAL LOCAL REGULATORY AUTHORITY 
Pharmacy and Poisons Board (PPB),  
Expert Committee on Clinical Trials (ECCT) 
P.O. Box 27663, Lenanna Road  
Nairobi, Kenya 00506 


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 REGULATORY REPORTING 
10.2.1 IMMEDIATE AND CONTINUING REVIEW REPORTING TO THE DOD 
The DoD research monitor should also review the related SAEs, deaths, and unanticipated 
problems involving risks to subjects or others and provide an independent assessment to the 
WRAIR IRB (as a DoD research monitor’s report). 
Reports will be submitted within 48 hours to the WRAIR IRB by phone at 301-319-9940, or by 
email (usarmy.detrick.medcom-wrair.mbx.hspb@mail.mil).  The PI or designee will then submit 
written reports within ten working days to the WRAIR IRB at the following address: Walter Reed 
Army Institute of Research, ATTN: Human Subject Protection Branch (HSPB), 503 Robert Grant 
Ave, Silver Spring, MD 20910. 
Follow up reports will be submitted as additional information becomes available.  A summary of 
the non-serious adverse events and the SAEs (both related and unrelated) that occurred during the 
reporting period should also be included in the continuing review report to the WRAIR IRB.  The 
WRAIR HSPB will report SAEs to the USAMRDC, ORP, HRPO as per UWZ-C-636. 
All serious unanticipated problems involving risk to participants or others (UPIRTSOs) should 
promptly (within 48 hours) reported by telephone, or by email to the WRAIR IRB and the DAIDS 
MO. Prompt reporting should be submitted to the WRAIR IRB by phone at 301-319-9940, or by 
email usarmy.detrick.medcom-wrair.mbx.hspb@mail.mil.  The Principal Investigator will then 
submit written reports within ten working days to the WRAIR IRB at the following address: Walter 
Reed Army Institute of Research, ATTN: Human Subject Protection Branch, 503 Robert Grant 
Ave, Silver Spring, MD 20910 and the KEMRI SERU.  The WRAIR HSPB will report to 
USAMRDC, ORP, HRPO as per SOP UWZ-C-636.  
Follow up reports should be submitted as soon as additional information becomes available.  A 
summary of the serious unanticipated problems should also be included in the continuing review 
report submitted to the KEMRI SERU, and the WRAIR IRB. 
The DoD research monitor should also review the unanticipated events and provide an independent 
assessment to the WRAIR HSPB (as a DoD research monitor’s report).  WRAIR HSPB will report 
these summaries to the USAMRDC, ORP, HRPO.  MHRP COO will forward the report to the 
Division of AIDS (DAIDS). 
10.2.2 REPORTING AND MANAGEMENT OF PARTICIPANTS WHO BECOME PREGNANT 
Pregnant women are excluded from enrollment, however, if a participant becomes pregnant during 
the study, further vaccinations will be stopped, and she will be referred for maternal and child 
health services.  Participants will continue to be followed for the remainder of the study period for 
safety, and the study team will follow the course of the pregnancy until the outcome is documented.  
During subsequent study visits, blood draws (6 mLs for basic chemistry and hematology) will be 
conducted for safety evaluations only.  No optional collections or procedures will be performed. 


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The PI or designated associate investigator will be responsible for reporting any pregnancy to the 
PSRT and the study database.  The PSRT will review this information.  The site PI will forward 
notification as necessary to the WRAIR IRB and KEMRI SERU. 
Pregnancy outcomes will be recorded via a standardized case report form.  Information 
documented on this form will include the date of last menstrual period, the date that the pregnancy 
was confirmed, any history of complications during prior pregnancies (such as congenital 
abnormalities or spontaneous abortions), and the outcome of the pregnancy including date of 
termination or delivery, any complications of pregnancy, and the status of the child.  A separate 
case report form will be completed for the delivered child to document date of delivery, gender, 
weight, the presence of any congenital abnormalities, American Pediatric Gross Assessment 
Record (APGAR) score, HIV status, and any other complication of delivery. 
10.2.3 REPORTING AND MANAGEMENT OF PARTICIPANTS WHO BECOME INCARCERATED 
Participation of prisoners is not planned, and any participant will be suspended from study visits 
while incarcerated, except visits or telephone contact for ensuring participant safety.  No study 
product will be administered to a participant who is incarcerated.  The IRB will be notified of the 
period of incarceration.  Data and samples that were collected before the period of incarceration 
may still be stored and used for analyses.  After release from incarceration, either the participant 
may return to participation in study visits according to the SOE or study participation may be 
terminated at the discretion of the PI. 
Any participant who is incarcerated will be re-consented before rejoining the study. 
10.2.4 SOCIAL HARMS REPORTING 
Unanticipated events and social harms may occur during the study.  When such events are related 
to study participation, the study staff, informed of these events, will inform the PI or designee.  
The PI or delegated associate investigator will then prepare a narrative summary of the event and 
report to KEMRI SERU, MHRP COO, and PSRT including DAIDS Medical Officer.  WRAIR 
IRB will then be informed.  The DoD research monitor should also review the social harms and 
provide an independent assessment of these to the WRAIR HSPB.  WRAIR HSPB will report 
these summaries to the USAMRDC, ORP, HRPO. 
 PROTOCOL DEVIATIONS 
It is the responsibility of the site principal investigator and personnel to use continuous vigilance 
to identify and report deviations. A protocol deviation is any noncompliance with the clinical trial 
protocol, GCP, or protocol-specific MOP requirements.  The noncompliance may be either on the 
part of the participant, the site principal investigator, or the site personnel.  Because of deviations, 
corrective actions are to be developed by the site and implemented promptly. 
The investigator should not implement any deviation from, or changes of the protocol without 
agreement by the sponsor and prior review and documented approval from the IRB/IEC of an 
amendment, except where necessary to eliminate an immediate hazard to trial participants. 


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All protocol deviations (PD), as defined above, must be addressed in study participant data 
collection forms.  The principal investigator and personnel are responsible for knowing and 
adhering to their IRB requirements. 
The procedures for handling protocol deviations will occur as follows: the study staff will notify 
the PI as soon as possible if he or she is not present when the deviation is discovered.  Any PD 
resulting in unanticipated problems that put participants or others at risk will be reported as an 
UPIRTSO. 
The timeline for reporting protocol deviations to the WRAIR IRB is determined by the 
categorization of the deviation: (1) major or (2) minor. 
10.3.1 MAJOR  
A major deviation also known as protocol violation is non-adherence to the IRB approved protocol 
that has the potential to affect the rights and welfare of the research participant, to increase the risk 
to the research participant, to change the willingness of the volunteer to continue participation, or 
to compromise the integrity of the study data in such a way that the study objectives may not be 
achieved.   
Examples of major deviation include exceptions to eligibility criteria, exceptions to the form and 
manner of obtaining informed consent, and exceptions to the schedule of administration of an 
investigational product.   
Major deviations must be promptly reported (within 48 hours upon the PI becoming aware of the 
event) to DAIDS and the WRAIR IRB (via the COO) and the KEMRI SERU, as well as recorded 
in the study deviation log.  Notification that a major deviation occurred should be submitted to the 
WRAIR HSPB by phone at 301-319-9940, or by email (usarmy.detrick.medcom-
wrair.mbx.hspb@mail.mil).  The PI will then submit a written report within ten working days to 
the WRAIR IRB (via the COO) at the following address: Walter Reed Army Institute of Research, 
ATTN: Human Participants Protection Branch, 503 Robert Grant Ave, Silver Spring, MD 20910 
and the KEMRI SERU.  
10.3.2 MINOR 
Minor deviations are departures from the protocol that do not affect or potentially affect the health 
and welfare of study participants, and do not compromise the integrity of the results in such a way 
that the study objectives may not be achieved, although they may nonetheless affect the study 
results.   
Examples of minor deviations include follow up visits occurring outside the protocol required time 
frame because of the participant’s schedule, or blood samples being obtained at times close to but 
not precisely at the time points specified in the protocol. 
Minor deviations will be reported to KEMRI SERU and WRAIR IRB as part of the protocol 
continuing review report and should be reported in the deviation log.  Major deviations should also 
be summarized in the continuing review reports.  


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Knowledge of any instances of serious or continuing non-compliance with the regulations or 
requirements will be reported immediately to the KEMRI SERU and the WRAIR IRB.  The 
WRAIR HSPB will report the deviations and instances of noncompliance with the USAMRDC, 
ORP, HRPO as per SOP UWZ-C-636. 
 PROTOCOL AMENDMENTS 
All amendments and modifications will be submitted to the WRAIR IRB, KEMRI SERU and 
Kenya Pharmacy and Poisons Board (PPB) for review and approval.  No changes in protocol 
conduct will be implemented until approval is obtained from the WRAIR IRB, KEMRI SERU, 
and Kenya PPB unless required to eliminate apparent immediate hazards to the study participants.  
Amendments and modifications cannot be implemented until the USAMRDC, ORP, HRPO, as 
applicable, and the WRAIR Commander’s Authorization has been issued.  The WRAIR HSPB 
will submit amendments and modifications to the USAMRDC, ORP, HRPO as per SOP UWZ-C-
636.  
Upon receiving final IRB/EC and any other applicable approvals for an amendment, sites should 
implement the amendment immediately.  Sites are required to submit an amendment registration 
packet to the DAIDS PRO at the RSC.  Site-specific ICF(s) WILL NOT be reviewed and approved 
by the DAIDS PRO and sites will receive an Amendment Registration Notification from the 
DAIDS PRO that approves the site specific ICFs and indicates successful completion of the 
amendment protocol registration process.   A copy of the final amendment Registration 
Notification issued by the DAIDS PRO should be retained in the site's regulatory files. 
 CONTINUING REVIEWS AND CLOSEOUT REPORTS 
The PI is responsible for submitting the required continuing review reports and associated 
documents to the WRAIR IRB, KEMRI SERU and Kenya PPB, allowing enough time for review 
and continuation determination before the established continuing review date.  A closeout report 
will be submitted after ten years or upon completion of the study, whichever occurs first.  The 
WRAIR HSPB will submit continuing review and the closeout reports to the USAMRDC, ORP, 
HRPO as per SOP UWZ-C-636. 
 REGULATORY AUDITS 
The knowledge of any pending compliance inspection or visit by the US FDA, OHRP, Kenya PPB, 
or other government agency concerning clinical investigation or research, the issuance of 
Inspection Reports, FDA Form 483, warning letters or actions taken by any regulatory agencies 
including legal or medical actions and any instances of serious or continuing noncompliance with 
the regulations or requirements will be reported immediately to the sponsor (DAIDS) and WRAIR 
HSPB and KEMRI SERU.  The WRAIR HSPB will report knowledge of any pending 
inspections/audits by regulatory agencies to the USAMRDC, ORP, HRPO. 


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 ESSENTIAL AND SOURCE DOCUMENTS  
 SOURCE DOCUMENTS 
Source documents are original documents, data, and records from which the participant’s data are 
obtained. These include but are not limited to hospital records, clinical and office charts, laboratory 
and pharmacy records, diaries, radiographs, and correspondence. The diary card is not a source 
document but a memory aid for volunteers, as has been done with prior MHRP vaccine trials (e.g. 
RV306); the information gained from the review of the diary card and the interview with 
participants will be documented using a combination of progress notes and CRFs maintained in 
the participants research chart.   
 ESSENTIAL DOCUMENTS 
The participating site will maintain appropriate medical and research records in compliance with 
ICH E6 and regulatory and institutional requirements for the protection of confidentiality of 
subjects. The site will permit authorized representatives of the DAIDS, its designees, and 
appropriate regulatory agencies to examine (and when required by applicable law, to copy) clinical 
records for the purposes of quality assurance reviews, audits, and evaluation of the study safety 
and progress. These representatives will be permitted access to all source data and source 
documents, which include, but are not limited to, hospital records, clinical and office charts, 
laboratory notes, memoranda, or evaluation checklists, pharmacy dispensing records, recorded 
data from automated instruments, copies or transcriptions certified after verification as being 
accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, 
and subject files and records kept at the pharmacy, at the laboratories, and medico-technical 
departments involved in the clinical trial.  
The investigator and staff are responsible for ensuring maintenance of a comprehensive and 
centralized filing system of all study-related (essential) documentation, suitable for inspection at 
any time by representatives of the following: KEMRI SERU, PPB, USAMRDC, ORP, HRPO the 
NIAID, the FDA, the Kenya Ministry of Health, WRAIR, the people who work for these 
organizations, and other local, US or international regulatory agencies. Essential documents for all 
study participants are to be maintained by the investigators in a secure storage facility. Elements 
include: 
• Participant files containing completed informed consent forms, and copies of source 
documentation 
• Study files containing the protocol will include all amendments and copies of 
correspondence between the study site, protocol team and the IRB 
• All Essential Documents outlined in the ICH Good Clinical Practice Guideline. 
In addition, all original source documentation must be maintained and be readily available for 
monitoring or auditing purposes.  


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 ADMINISTRATIVE AND LEGAL OBLIGATIONS 
 CONDUCT OF THE RESEARCH STUDY 
This research study will be conducted per GCP, International Conference on Harmonization (ICH) 
guidelines, DoD Directive 3216.2, the Declaration of Helsinki, the Belmont Report, the U.S. Code 
of Federal Regulations 21 CFR 312, 812, 50 and 56, 45 CFR 46 and 32 CFR 219, and all applicable 
Kenyan laws and regulations. 
  PROTOCOL REGISTRATION 
12.2.1 INITIAL REGISTRATION 
Prior to implementation of this protocol, and any subsequent full version amendments, the site 
must have the protocol and the protocol informed consent forms approved, as appropriate, by 
KEMRI SERU and any other applicable regulatory entity (RE). Upon receiving final approval, 
sites will submit all required protocol registration documents to the DAIDS Protocol Registration 
Office (DAIDS PRO) at the Regulatory Support Center (RSC).  The DAIDS PRO will review the 
submitted protocol registration packet to ensure that all of the required documents have been 
received.  
The informed consent forms (ICFs) WILL be reviewed and approved by the DAIDS PRO and the 
site will receive an Initial Registration Notification from the DAIDS PRO that indicates successful 
completion of the protocol registration process. A copy of the Initial Registration Notification 
should be retained in the regulatory files. 
12.2.2 AMENDMENTS 
Upon receiving final IRB/EC and any other applicable RE approval(s) for an amendment, sites 
should implement the amendment immediately.  Sites are required to submit an amendment 
registration packet to the DAIDS PRO at the RSC.  The DAIDS PRO will review the submitted 
protocol registration packet to ensure that all the required documents have been received. The ICFs 
WILL NOT be reviewed and approved by the DAIDS PRO and the site will receive an Amendment 
Registration Notification when the DAIDS PRO receives a complete registration packet. A copy 
of the Amendment Registration Notification should be retained in the site regulatory files. 
For additional information on the protocol registration process and specific documents required 
for initial and amendment registrations, refer to the current version of the DAIDS Protocol 
Registration Manual. 
  COMPLIANCE WITH NIH GUIDELINES FOR RESEARCH INVOLVING 
PRODUCTS CONTAINING RECOMBINANT DNA 
Because this study is evaluating products containing recombinant DNA, per NIH Guidelines for 
Research Involving Recombinant DNA Molecules, the study must be submitted to the site 
Institutional Biosafety Committee (IBC) and must be approved before participants are enrolled at 


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each respective institution.  Investigators at each site are responsible for obtaining IBC approval 
and periodic review of the research per NIH guidelines section IV-B07-b-(6) and section IV-B-2-
b.  IBC review and approval must be documented by the investigator and submitted as part of 
protocol registration for this trial. 
The NIH guidelines also require that the Recombinant DNA Advisory Committee (RAC) must 
submit human gene transfer trials conducted at or sponsored by institutions that receive NIH funds 
to the NIH Office of Biotechnology Activities (OBA) for review.  The NIH guidelines create 
exceptions to RAC review for vaccines, which do not persist, and the RV460 Protocol team will 
submit a request for exemption with the study concept proposal for RAC review and response. 
 SPONSOR STUDY MONITORING 
Kericho site visits by study monitors will be made per the IND sponsor’s policy to monitor the 
following: study operations, the quality of data collected in the research records, the accuracy, and 
timeliness of data entered in the database, and to determine that all process and regulatory 
requirements are met.  
Kericho site investigators will allow the study monitors, DAIDS, the KEMRI SERU, Kenya PPB, 
WRAIR IRB, USAMRDC, ORP, HRPO, other DoD regulatory agencies, and the FDA to inspect 
study documents (e.g., consent forms, drug distribution forms, case report forms), and pertinent 
hospital or clinic records for confirmation of the study data.  
 BIOHAZARD CONTAINMENT 
As the transmission of HIV and other blood borne pathogens can occur through contact with 
contaminated needles, blood, and blood products, appropriate blood and secretion precautions will 
be employed by all personnel in the drawing of blood and shipping and handling of all specimens 
for this study, as currently recommended by the Centers for Disease Control and the National 
Institutes of Health.  All dangerous goods materials, including diagnostic specimens and infectious 
substances, must be transported using packaging mandated by CFR 42 Part 72. 
The International Air Transport Association Dangerous Goods Regulations for UN 3373, 
Biological Substance, Category B and Packing Instruction 650 will send all infectious specimens 
using packaging that meets requirements specified.  Refer to individual carrier guidelines (e.g., 
Federal Express or Airborne) for specific instructions. 
 EXPECTED APPLICATION OF RESULTS 
On completion, the study findings will be shared with all authorities having oversight of this 
protocol including the KEMRI SERU, Kenya PPB, WRAIR IRB, and Kenya’s Ministry of Health.  
Results obtained from this study may inform considerations for the development of an HIV vaccine 
for use in the prevention of HIV infection and to fulfill a US FDA application.  
The description of this study and the summary of results will be available on 
http://www.ClinicalTrials.gov.  


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Any new information from this study or other studies that may affect the participant’s health, 
welfare, or willingness to continue with the study will be given to the participant by the appropriate 
method of contact, i.e., the participant will be contacted as soon as possible if, likely by phone in 
the case of a significant lab abnormality.  The results of the study will be shared with the 
participants through a WRAIR IRB approved letter, at the participant’s written request.   
 USE OF INFORMATION AND PUBLICATION 
It is understood by the investigator that the information generated in this study may be used in 
connection with the development of the product and therefore may be disclosed to government 
agencies in various countries.  To allow for the use of information derived from the study, the 
investigator is obliged to provide the sponsor with complete test results, all study data, and access 
to all study records. Confidentiality of participants will be maintained by exclusion of personally 
identifiable information from the research database and from any publications that result.      
WRAIR recognizes the importance of communicating medical study data and therefore encourages 
their publication in reputable scientific journals and at seminars or conferences.  Any results of 
medical investigations and or publication/lecture/manuscripts based thereon shall be exchanged 
and discussed by the investigator, and the USAMRDC and sponsor prior to submission for 
publication or presentation.  Details of timelines are provided in Clinical Trial Agreements. 
Results from investigations shall not be made available to any third party by the investigating team 
outside the publication procedure as outlined previously.  WRAIR will not quote from publications 
by investigators in its scientific information and or promotional material without full 
acknowledgment of the source (i.e., author and reference).  All publications written by WRAIR 
investigators must be reviewed and approved by the WRAIR Office of Research Technology and 
Applications (ORTA). 
 VOLUNTEER REGISTRY DATA SHEET 
The USAMRDC requires that investigators complete data sheets on all participants participating 
in this protocol for entry into the Command's Volunteer Registry Database.  This Volunteer 
Registry Database Sheet (VRDS) contains items of personal information, such as participant name, 
address, national identification number, study identity, and dates of participation.  
The intent of this database is twofold: first, to readily answer questions about an individual's 
participation in research sponsored by the USAMRDC; and second, to ensure that USAMRDC 
can exercise its obligation to ensure that all research study participants are adequately warned (duty 
to warn) of risks and to provide new information as it becomes available.  This information will 
be stored at USAMRDC for a minimum of 75 years and is kept confidential.  The Volunteer 
Registry Data Sheet is a separate form and is not linked to the study database. 


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 PRINCIPAL INVESTIGATOR AGREEMENT 
1. I will conduct the study entitled: “A Randomized, Double-Blind Phase 1 Trial to Evaluate 
the Safety and Immunogenicity of HIV-1 Clade C Env DNA Vaccine Alone, with Different 
Adjuvants or an Adjuvanted HIV-1 Clade C Recombinant gp145 C.6980 Protein Vaccine 
and then Boosted with the Adjuvanted gp145 C.6980 Vaccine Either with or without the 
Clade C Env DNA Vaccine in Healthy HIV Uninfected Adults in Kenya: in accordance 
with the provisions of this protocol and all applicable protocol-related documents. I agree 
to conduct this study in compliance with United States (US) Health and Human Service 
regulations (45 CFR 46 and 32 CFR 219); applicable U.S. Food and Drug Administration 
regulations; standards of the International Conference on Harmonization Guideline for 
Good Clinical Practice (E6); Institutional Review Board/Ethics Committee determinations; 
all applicable in-country, state, and local laws and regulations; and other applicable 
requirements (e.g., US National Institutes of Health, Division of AIDS) and institutional 
policies. 
2. I agree to follow this protocol version as approved by the IRBs/ERCs.  
3. I will conduct the study in accordance with applicable IRB/ERC requirements, Federal 
regulations and state and local laws to maintain the protection of the rights and welfare of 
study participants.  
4. I certify that I, and the study staff, have received the requisite training to conduct this 
research protocol.  
5. I will not modify the protocol without first obtaining an IRB/ERC approved amendment 
and new protocol version unless it is necessary to protect the health and welfare of study 
participants.  
6. I have read and understood the information in the Investigators’ Brochure regarding the 
risks and potential benefits.  I agree to conduct the protocol in accordance with Good 
Clinical Practices (ICH-GCP), the applicable ethical principles, the Statement of 
Investigator (Form FDA 1572), and with local regulatory requirements.   
7. I will ensure that the data and specimens are maintained in accordance with the data and or 
specimen disposition outlined in the protocol.  Any modifications to this plan should first 
be reviewed and approved by the applicable IRBs/ERCs.   
8. I will promptly report changes to the research or unanticipated problems immediately to 
the KEMRI SERU at 254 020 2722541 and WRAIR IRB via the WRAIR Human 
Participants Protection Branch at 301-319-9940 (during duty hours) or to the 
usarmy.detrick.medcom-wrair.mbx.hspb@mail.mil and submit a written report within 10 
working days of knowledge of the event.  
9. I will prepare continuing review reports at an interval established by the IRB/ERC, and a 
study closure report when all research activities are completed.  


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10. I will immediately report to the KEMRI SERU and WRAIR Human Participants Protection 
Branch knowledge of any pending compliance inspection by any outside governmental 
agency.  
11. I agree to maintain adequate and accurate records in accordance with IRB policies, Federal, 
state and local laws and regulations. 
 
RV460 Principal Investigator’s Name: Josphat Kosgei, MBChB, MSc 
Signature:  ………………………………………………. Date: _____/______/_______ 


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Guerena-Burgueno, F., et al., Safety and immunogenicity of a prototype enterotoxigenic 
Escherichia coli vaccine administered transcutaneously. Infect Immun, 2002. 70(4): p. 
1874-80. 
55. 
Behrens, R.H., et al., Efficacy and safety of a patch vaccine containing heat-labile toxin 
from Escherichia coli against travellers' diarrhoea: a phase 3, randomised, double-blind, 
placebo-controlled field trial in travellers from Europe to Mexico and Guatemala. Lancet 
Infect Dis, 2014. 14(3): p. 197-204. 
56. 
Glenn, G.M., et al., Safety and immunogenicity of an influenza vaccine A/H5N1 
(A/Vietnam/1194/2004) when coadministered with a heat-labile enterotoxin (LT) 
adjuvant patch. Vaccine, 2009. 27 Suppl 6: p. G60-6. 
57. 
McKenzie, R., et al., Transcutaneous immunization with the heat-labile toxin (LT) of 
enterotoxigenic Escherichia coli (ETEC): protective efficacy in a double-blind, placebo-
controlled challenge study. Vaccine, 2007. 25(18): p. 3684-91. 
58. 
El-Kamary, S.S., et al., Safety and immunogenicity of a single oral dose of recombinant 
double mutant heat-labile toxin derived from enterotoxigenic Escherichia coli. Clin 
Vaccine Immunol, 2013. 20(11): p. 1764-70. 
59. 
Lundgren, A., et al., Safety and immunogenicity of an improved oral inactivated 
multivalent enterotoxigenic Escherichia coli (ETEC) vaccine administered alone and 
together with dmLT adjuvant in a double-blind, randomized, placebo-controlled Phase I 
study. Vaccine, 2014. 32(52): p. 7077-84. 


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60. 
Lundgren, A., M. Jertborn, and A.M. Svennerholm, Induction of long term mucosal 
immunological memory in humans by an oral inactivated multivalent enterotoxigenic 
Escherichia coli vaccine. Vaccine, 2016. 34(27): p. 3132-3140. 
61. 
Tennant, S.M., A.D. Steele, and M.F. Pasetti, Highlights of the 8th International 
Conference on Vaccines for Enteric Diseases: the Scottish Encounter To Defeat 
Diarrheal Diseases. Clin Vaccine Immunol, 2016. 23(4): p. 272-81. 
62. 
Clements, J.D. and E.B. Norton, The Mucosal Vaccine Adjuvant LT(R192G/L211A) or 
dmLT. mSphere, 2018. 3(4). 
63. 
Rerks-Ngarm, S., et al., Randomized, Double-Blind Evaluation of Late Boost Strategies 
for HIV-Uninfected Vaccine Recipients in the RV144 HIV Vaccine Efficacy Trial. The 
Journal of infectious diseases, 2017. 215(8): p. 1255-1263. 
64. 
Easterhoff, D., et al., Boosting of HIV envelope CD4 binding site antibodies with long 
variable heavy third complementarity determining region in the randomized double blind 
RV305 HIV-1 vaccine trial. PLOS Pathogens, 2017. 13(2): p. e1006182. 
65. 
Summerton, N.A., et al., Toward the development of a stable, freeze-dried formulation of 
Helicobacter pylori killed whole cell vaccine adjuvanted with a novel mutant of 
Escherichia coli heat-labile toxin. Vaccine, 2010. 28(5): p. 1404-11. 
66. 
Sjokvist Ottsjo, L., et al., A double mutant heat-labile toxin from Escherichia coli, 
LT(R192G/L211A), is an effective mucosal adjuvant for vaccination against Helicobacter 
pylori infection. Infect Immun, 2013. 81(5): p. 1532-40. 
67. 
Bansal, A., et al., Multifunctional T-cell characteristics induced by a polyvalent DNA 
prime/protein boost human immunodeficiency virus type 1 vaccine regimen given to 
healthy adults are dependent on the route and dose of administration. J Virol, 2008. 
82(13): p. 6458-69. 
68. 
Flynn, N.M., et al., Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 
vaccine to prevent HIV-1 infection. J Infect Dis, 2005. 191(5): p. 654-65. 
69. 
Spearman, P., et al., A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits 
potent neutralizing antibodies but limited breadth of neutralization in human volunteers. 
J Infect Dis, 2011. 203(8): p. 1165-73. 
70. 
Gray, G.E., et al., Subtype C gp140 Vaccine Boosts Immune Responses Primed by the 
South African AIDS Vaccine Initiative DNA-C2 and MVA-C HIV Vaccines after More 
than a 2-Year Gap. Clin Vaccine Immunol, 2016. 23(6): p. 496-506. 
71. 
Huang, Y., et al., Selection of HIV vaccine candidates for concurrent testing in an 
efficacy trial. Curr Opin Virol, 2016. 17: p. 57-65. 


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72. 
Heppner, D.G., et al., Safety, immunogenicity, and efficacy of Plasmodium falciparum 
repeatless circumsporozoite protein vaccine encapsulated in liposomes. J Infect Dis, 
1996. 174(2): p. 361-6. 
73. 
Harris, D.T., et al., Immunologic approaches to the treatment of prostate cancer. Semin 
Oncol, 1999. 26(4): p. 439-47. 
74. 
Zollinger, W.D., et al., Phase I study of a Neisseria meningitidis liposomal vaccine 
containing purified outer membrane proteins and detoxified lipooligosaccharide. 
Vaccine, 2012. 30(4): p. 712-21. 
75. 
Beck, Z., et al., Immune response to antigen adsorbed to aluminum hydroxide particles: 
Effects of co-adsorption of ALF or ALFQ adjuvant to the aluminum-antigen complex. 
Journal of Controlled Release, 2018. 275: p. 12-19. 
76. 
Gamble, L.J. and Q.L. Matthews, Current progress in the development of a prophylactic 
vaccine for HIV-1. Drug design, development and therapy, 2010. 5: p. 9-26. 
77. 
Ling Munier, C.M., C.R. Andersen, and A.D. Kelleher, HIV Vaccines. Drugs, 2011. 
71(4): p. 387-414. 
78. 
Moody, M.A., Modulation of HIV-1 immunity by adjuvants. Curr Opin HIV AIDS, 2014. 
9(3): p. 242-9. 
79. 
ClinicalTrials.gov. 
https://clinicaltrials.gov/ct2/results?cond=HIV&term=aluminum&cntry=&state=&city=
&dist=. 
80. 
Haynes, B.F., et al., Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial. 
New England Journal of Medicine, 2012. 366(14): p. 1275-1286. 
81. 
Gupta, R.K., et al., Adjuvants--a balance between toxicity and adjuvanticity. Vaccine, 
1993. 11(3): p. 293-306. 
82. 
Edelman, R., An Overview of Adjuvant Use, in Vaccine Adjuvants: Preparation Methods 
and Research Protocols, D.T. O’Hagan, Editor. 2000, Springer New York: Totowa, NJ. 
p. 1-27. 
83. 
Gherardi, R.K., et al., Macrophagic myofasciitis lesions assess long-term persistence of 
vaccine-derived aluminium hydroxide in muscle. Brain, 2001. 124(Pt 9): p. 1821-31. 
84. 
Scharton-Kersten, T., et al., Transcutaneous immunization with bacterial ADP-
ribosylating exotoxins, subunits, and unrelated adjuvants. Infect Immun, 2000. 68(9): p. 
5306-13. 
85. 
Frech, S.A., et al., Improved immune responses to influenza vaccination in the elderly 
using an immunostimulant patch. Vaccine, 2005. 23(7): p. 946-50. 


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86. 
Frech, S.A., et al., Use of a patch containing heat-labile toxin from Escherichia coli 
against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled 
field trial. Lancet, 2008. 371(9629): p. 2019-25. 
87. 
Glenn, G.M., et al., Transcutaneous immunization with heat-labile enterotoxin: 
development of a needle-free vaccine patch. Expert Rev Vaccines, 2007. 6(5): p. 809-19. 
88. 
UNAIDS Data 2017, J.U.N.P.o.H.A. (UNAIDS), Editor. UNAIDS 2017. 
89. 
WHO. Global Health Observatory (GHO) data HIV/AIDS. 2018  [cited 2018 12NOV]. 
90. 
UNAIDS, Report on the Global AIDS Epidemic: Global Report 2013. 
91. 
CDC, Centers for Disease Control and Prevention in HIV Surveillance Supplemental 
Report. 2012. 
92. 
Jaworski, J.P., et al., Co-immunization with multimeric scaffolds and DNA rapidly 
induces potent autologous HIV-1 neutralizing antibodies and CD8+ T cells. PloS one, 
2012. 7(2): p. e31464-e31464. 
93. 
Patel, V., et al., DNA and virus particle vaccination protects against acquisition and 
confers control of viremia upon heterologous simian immunodeficiency virus challenge. 
Proc Natl Acad Sci U S A, 2013. 110(8): p. 2975-80. 
94. 
Patricia D'Souza, M., et al., Innovative approaches to track lymph node germinal center 
responses to evaluate development of broadly neutralizing antibodies in human HIV 
vaccine trials. Vaccine, 2018. 36(38): p. 5671-5677. 
95. 
Guerena-Burgueno, F., Safety and Immunogenicity of a Prototype Enterotoxigenic 
Escherichia coli Vaccine Administered Transcutaneously. Infection and Immunity, 2002. 
70(4): p. 1874-1880. 


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 KERICHO BUDGET AND TIMEFRAME 
 KERICHO BUDGET  
 
Item 
Total Cost (USD) 
1 Personnel 
113,645 
2 Equipment 
56,976 
3 Supplies (test kits, clinic and lab supplies, office consumables, and 
other study related supplies)  
431,607 
4 Travel (Domestic and Foreign) 
83,116 
5 Travel Training (Domestic and Foreign)  
14,500 
6 Other Expenses 
193,004 
7 Overheads (HJF MRI) 
68,481 
8 Overheads (HJF) 
9,613 
9 Other overheads 
78,095 
TOTAL BUDGET 
1,049,037 
15.1.1 KERICHO BUDGET JUSTIFICATION 
15.1.1.1 
Personnel 
The amount allocated will provide salary support (and benefits to hired employees) to the Deputy 
Director of KEMRI and clinical research site leader in Kericho, and to the site PI and associate 
investigator, the Laboratory Director, Study Coordinator, Research Nurse, Pharmacist, Data 
Manager, Data QA/QC, Data entry specialist, a Regulatory staff and Finance Manager to assist 
with the study.  
15.1.1.2 
Equipment  
The budget allocated for equipment is to purchase an ultra-low upright freezer and nitrogen tank 
to store patient samples in Year 3 of the study. 
15.1.1.3 
Supplies 
The budget covers for laboratory, clinic and general supplies, to include test kits, reagents, quality 
control standards required by the protocol, specimen collection kits, tubes, pipets and pipet tips 
and other processing supplies.  Office supplies include notebooks, pens, pencils, markers, labeling 
supplies and other materials for data collections and study execution including.  General supplies 
cover operational expenses such as gasoline for travel, vehicle maintenance, fuel for backup 
generators, utilities and clinic security. 
15.1.1.4 
Travel 
Travel expenses include Community Advisory Board member transportation expenses for 
meetings, volunteer recruitment, volunteer transportation and retention, hotel and per diem for 
staff responsible for transportation and tracking (in case required) and PI, co-PI and associate 


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investigators travel to local conferences to present study data and meeting in the US with the study 
PI and other MHRP collaborators. 
15.1.1.5 
Other expenses 
This will cover expenses related to adverse event follow- up (in case needed) including referral to 
medical specialist (consultation and treatment), radiographic images or medications.  It also 
includes expenses for compensation of study participants for study visits and optional procedures. 
15.1.1.6 
Overheads 
Overhead includes those for HJF MRI and HJF.


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 TIME FRAME AND DURATION AT KERICHO 
Table 7: Time Frame and Duration at Kericho 
 


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 APPENDICES 


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SCHEDULE OF EVALUATIONS 


RV 460 Schedule of Evaluations
Visit Number
S1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26 Exit
Visit Day
-45 to -3
0
3 ± 1 
7 ± 2 
14 ± 3 
28 ± 7 
35 ± 2 
42 ± 3 
84 ± 7 
87 ± 1
91 ± 2
98 ± 3
140 ± 7
143 ± 1
147 ± 2
154 ± 3
224 ± 7 
231 ± 2
238 ± 3
392 ± 7 
395 ± 1
399 ± 2
406 ± 3
476 ± 14
560 ± 14
728 ± 14
735 ± 14
Visit week
0
0.5
1
2
4
5
6
12
12.5
13
14
20
20.5
21
22
32
33
34
56
56.5
57
58
68
80
104
105
Clinical
Breifing & contact information 
X
Informed consents
X
Test of understanding
X
Complete physical exam, height, 
weight & review medical history 
X
Vital signs (BP, pulse, RR, oral 
temp)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant Medication
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Targeted physical exam and review 
of symptoms
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
HIV risk counseling; pregnancy 
counseling11
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Vaccination13
X 6
X 6
X 6
X 6
X 6
X 6
Review Eligbility
X
X
X
X
X
X
Enrollment and randomization12
X
Assess reactogenicity in clinic 30-
60 min post-vaccination
X
X
X
X
X
X
MAAE documentation 9
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Event documentation
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Diary card completion/review 10
X
X
X
X
X
X
X
X
X
X
Clinical Laboratory Assessments 
5
Urinalysis dipstick for blood, 
protein and glucose
X
Urine pregnancy test 7
X
X
X
X
X
X2
X
X
X
X
X
X2
X
X
X
CBC with differential
3
3
3
3
3
3
3
Creatinine, ALT, AST
3
3
3
3
3
3
3
Syphilis serology
6
HBsAg/HepC
NB
Pap smear for Softcup collection 
participants
X
Coagulation and safety tests prior 
lymph node biopsy8
9
9
HIV testing with Pre/Post HIV test 
counseling
6
6
6
6
6
6
6
6
Research Laboratory 
Assessments 3
HIV NAb
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
Binding antibody/antibody profiling
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
6
Functional Antibody Assays 
(ADCC, ADCP, ADCVI, etc)
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
Cellular immune analysis
93.5
17
17
42.5
25.5
42.5
17
34
85
17
34
68
34
68
17
34
85
85
85
85
34
Cytokine/soluble factor assays
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
NB
Gene expression/transcriptome 
analysis
34
17
17
17
8.5
17
17
17
17
8.5
Mucosal secretion collection 1, 7
X
X
X
X
X
X
X
X
X
Lymph node biopsy 2
X
X
Storage & additional 
immunogenicity testing (mL) 
25.5
17
17
8.5
17
8.5
34
17
34
17
17
51
25.5
25.5
25.5
17
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RV 460 Schedule of Evaluations
Visit Number
S1
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26 Exit
Visit Day
-45 to -3
0
3 ± 1 
7 ± 2 
14 ± 3 
28 ± 7 
35 ± 2 
42 ± 3 
84 ± 7 
87 ± 1
91 ± 2
98 ± 3
140 ± 7
143 ± 1
147 ± 2
154 ± 3
224 ± 7 
231 ± 2
238 ± 3
392 ± 7 
395 ± 1
399 ± 2
406 ± 3
476 ± 14
560 ± 14
728 ± 14
735 ± 14
Visit week
0
0.5
1
2
4
5
6
12
12.5
13
14
20
20.5
21
22
32
33
34
56
56.5
57
58
68
80
104
105
Daily volume (mL) 4, 5
18
171
34
23
77.5
29
31.5
60.5
37.5
34
49
134.5
37.5
34
40
126
29
40
126
46
34
66
168.5
122.5
128.5
128.5
63
Cumulative volume (mL) 4, 5
18
189
223
246
323.5
352.5
384
444.5
482
516
565
699.5
737
771
811
937
966
1006
1132
1178
1212
1278
1446.5
1569
1697.5
1826
1889
8 week cumulative volume 4, 5
444.5
158.5
163.5
212.5
315.5
292.5
289
295
372
29
69
195
46
80
146
314.5
122.5
128.5
128.5
191.5
7: Pregnancy testing must be performed prior to vaccination and mucosal secretion collection
8: 9ml should be taken if CBC/Chem results not available on day of biopsy. Otherwise, 3ml should be drawn
9: Medically Attended Adverse Events will be followed through the end of the study, a full 12 months following the last vaccination
10: Participants will take home the diary card and complete and the diary card will be reviewed at 7 days after vaccination.
11: Additional testing as clinically indicated
12: A participant is considered enrolled into the study once they are randomized into a study group
13: Study vaccination outside of a participant’s vaccination window may occur at the discretion of the PSRT.
4: The maximum amount drawn in any 8 week interval is 444.5 mL. The maximum amount drawn in one day is 171 mL. 
5: Clinical labs may be repeated if clinically significant.
6: Phone or clinic visit will be done to assess the participants well-being 24 hours (+1 day) after each vaccination. 
NB=No extra blood required
1: Mucosal secretion collections - Rectal secretions collected by sponge. Male participants: semen collection by masturbation. Female participants: cervicovaginal secretions collected by Softcup.
for menstruating females, mucosal collection window can be extended to -3 + 14 days.
2: Excisional inguinal lymph node biopsies will be performed in a subset of  participants who agree to undergo this procedure. Urine pregnancy testing prior to procedure. Biospsy site assessment at 7 days (+2 days) after each biopsy. 
3: Research labs may be performed at any visit where sufficient stored samples are available.
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 MAIN INFORMED CONSENT FORM 


RV460 / WRAIR #2672 
 
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Version 4.0  
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Main Informed Consent 
Page 1 of 17 
Kenya Medical Research Institute (KEMRI)  
United States Army Medical Research Directorate-Africa (USAMRD-A) 
In Collaboration with 
US Military HIV Research Program and the 
US Department of Defense (DoD) 
 
WRAIR #2672/RV460 Main Informed Consent Form 
 
Protocol Title: 
A Randomized, Double-Blind Phase 1 Trial to Evaluate the Safety and 
Immunogenicity of Priming with Env-C Plasmid DNA Vaccine Alone, 
with Different Adjuvants, or with an Adjuvanted HIV Env gp145 C.6980 
Protein Vaccine and Boosting with the Adjuvanted HIV Env gp145 
C.6980 Protein Vaccine with or without the Env -C Plasmid DNA Vaccine 
in Healthy HIV Uninfected Adults in Kenya 
Sponsor: 
National Institute of Allergy and Infectious Diseases (NIAID), Division 
of AIDS (DAIDS) Bethesda, Maryland US  
 
Funding: 
United States Army Medical Research Acquisition Activity  
U.S. Military HIV Research Program   
Henry M. Jackson Foundation for the Advancement of Military Medicine  
 
Site: 
 
Kenya Medical Research Institute (KEMRI) US Army Medical Research 
Directorate-Africa (USAMRD-A), Kericho, Kenya 
 
Principal 
Investigator:  
Dr. Josphat Kosgei, MBCHB, MSc 
 
Introduction 
You are being asked to take part in a research study, also called a clinical trial. This study 
involves research and you should know that research is not the same as medical care.  Research 
answers scientific questions and answers to these questions can help find new medicines, 
treatments, vaccines, and even knowledge on how the human body works.  
 
This study is supported by the United States (US) Department of Defense and several other 
organizations.  The box below tells you important things you should think about before deciding 
to join the study.  We will provide more detailed information below the box. Please ask questions 
about any of the information before you decide whether to participate. You may also wish to talk 
to others (for example, your family, friends, or your doctor) about this study, before agreeing to 
join.   
 
 
 
 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 4.0  
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Main Informed Consent 
Page 2 of 17 
 
Key Information for You to Consider 
• Voluntary Consent. You are being asked to volunteer for a research study.  It is up to you 
whether you choose to participate or not.  There are no penalties and you will not lose 
anything if you decide not to join or if after you join, you decide to quit.   
• Purpose. We are doing this research to test a vaccine for HIV and vaccine additives called 
adjuvants that can help the vaccine be more effective.  
• Duration. Your part of the study will last 105 weeks (26 months).  You will be asked to 
complete at least 26 clinic visits.  Additionally, you will be contacted by phone, once per 
week for three weeks to discuss any changes you may have experienced after the first 105 
weeks of being in the study. 
• Procedures and Activities. We will ask you to receive 6 doses of the experimental 
vaccines and monitor your blood and symptoms after each vaccine.   
• Risks. Most studies have some possible harms that could happen to you if you join.  In this 
study, we expect you to have some mild or moderate symptoms like what happens after 
you receive some approved vaccines. Some examples of mild common and expected 
reactions are fever, body aches, feeling tired and pain at the injection site.  Very rare but 
possible to have a serious and life-threatening allergic reaction right after a vaccine is 
given.  Additionally, there is a chance that you could develop a serious illness such as 
autoimmune disease, but this is also very rare.  
• Benefits. You will not directly benefit from participating in this study.  The results of this 
study will be shared with researchers from around the world and could play a role in future 
HIV vaccine development which may be beneficial in the future for others. None of the 
experimental HIV vaccine combination groups have been shown that they work to protect 
against HIV infection. Also, there is a possibility that you may be assigned to receive the 
inactive vaccine 
• Alternatives. Participation is voluntary, and the only alternative is to not participate. 
 
Please contact one of the below if you have any questions concerning the study or if you have 
any other questions or concerns.  
 
If you have questions about this study or if you have any symptoms that you think may 
be related to this study, contact: 
 
Dr. Josphat Kosgei, 
MBCHB, MSc  
 
Office: 
(0)5220 36302 
 
Mobile:  
(0)729 110 122 
 
Staff:  
(0) 5220) 36000/100 
 
Or 
 
Rael Bor, BSc 
Office: 
(0)5220 36329 
Mobile:  
0729110121 
Staff:  
(0) 5220) 36000/100 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 4.0  
17 May 2021 
Main Informed Consent 
Page 3 of 17 
 
1. 
Why are we doing this research? 
Researchers are doing this study to test an experimental vaccine for HIV.  A vaccine is a medical 
product given to prevent certain infectious diseases, most often caused by a virus or bacteria 
(germs). A vaccine may teach the human body to form a defensive response to try to prevent the 
disease from beginning or taking hold of the body. This defensive response is called the immune 
response, and it is the body’s way to fight infections. The study also tests different adjuvants. An 
adjuvant is a substance added to vaccines that can help to make the vaccine more effective by 
improving the immune response or causing the immune response to last longer than without the 
adjuvant.   
You are being asked to take part in this research study because you are a healthy adult and your 
participation will help researchers find out whether the experimental vaccines with adjuvants 
used in this study are safe causing mild side effects that are common, "expected" symptoms, 
fever, sore arm at injection site, or if the experimental vaccines cause unexpected reactions.  The 
data we record from the symptoms you tell help tell us if it is safe enough for other people.  We 
also want to gather information about if and how humans respond (develop immune responses) 
to the experimental vaccines, and how long the effects of the experimental vaccines last; we can 
learn that from your blood samples.  
Also, this study will compare the effects (both good and bad) of the study experimental vaccines 
with adjuvants and adjuvant patch to those of placebo injections and adjuvant skin patch. 
A placebo is a treatment for a disease or condition which is deliberately ineffective and allows 
researchers to compare the injection with active protection with the injection that has inactive 
(not protective) substance.  The placebo will consist of saline (sterile saltwater), and will be 
given the same way, but will have no active vaccine or adjuvant in it. It will look just like the 
experimental vaccines so that you and the study doctors will not know if you received the 
placebo or active vaccine.   
People who have received study experimental vaccines in other studies have still became 
infected with HIV when exposed to the virus. You must avoid any activities that might expose 
you to HIV. 
2. 
How do I join this study? 
If you agree to participate, you will have a screening visit which includes some lab tests, review 
of your health history and a physical exam.  After your test results are available, the researchers 
will review the results to determine if you meet the eligibility requirements to join this study. 
You may take this consent form home and discuss the study with your family or friends to help 
you decide if this is right for you.  Ask the study staff about the study schedule to plan on a time 
to return to enroll. 
 
At the screening visit you will:  
 
• Attend a briefing to learn about the study and provide your contact information 


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• Sign the informed consent forms 
• Take a short test to check if you understand the study.  To be eligible, you must 
answer 9 out of 10 questions correctly but you can take the test 3 times. 
• Meet with a doctor to review your medical history 
• Have a physical exam including vital signs 
• Have blood drawn (18 ml which is a little more than 1 Tablespoon) to test for HIV, 
Hepatitis B, Hepatitis C, syphilis, and your general health 
• Provide a urine sample for general health tests and pregnancy test for women 
You may be allowed to participate in the study if you meet the following requirements:   
• Healthy, male and female participant aged 18 to 40 years and available for 26 months  
• Low risk for HIV infection  
• Able to read English or Kiswahili.  
• Must agree to a home visit 
• Not pregnant or breastfeeding 
You are not allowed to participate in this study if any of the following criteria apply to you:   
• Have not been a sexually active MSM or transgender person in the last 6 months 
• Have ever had a serious reaction to vaccines or other substances 
• Regularly take certain medications that could affect your immune system 
• Have received the CERVARIX vaccine against HPV 
• Take or took anti-tuberculosis medication in the past 90 days  
• Have certain skin conditions 
 
3. 
What will I need to do during this study? 
If you are found to be qualified to participate in the study, you will be booked to come for an 
appointment for enrollment and you will be selected by chance to one of the seven (7) study 
groups.  
Additionally, as part of this study, you will have the choice to participate in the following 
additional optional collections:  
 
• Cervicovaginal secretion collections (women) 
• Semen collections (men) 
• Rectal secretion collections 
• Lymph node biopsies 


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These collections will be explained to you in a separate informed consent form.  You will have 
the opportunity then to ask any questions about these collections and you will not need to say yes 
to them to enroll in the study and you can change your mind at any time. 
It is important to remind you that to participate in this study, you have agreed to possible home 
visits by the study staff, and to be identified by a document with your photograph or fingerprint. 
Experimental vaccine visits: 
There are six (6) visits where you will receive an experimental vaccine. Vaccines will be given 
on study days 0, 28, 84, 140, 224 and 392.  However, a study vaccination may be given outside 
your vaccination window if the protocol safety review team (PSRT) permits.  At each of these 
visits, eligibility criteria will be reviewed again. You will be asked how you are feeling and if 
you are taking any medicines. Before the experimental vaccination, you will be asked to donate a 
blood sample to assess your general heath, test for HIV (at visit 1), and for research. Urine will 
also be collected for pregnancy testing if you are female. 
If you are assigned to Groups 3 or 4, you will be receiving a patch with the experimental vaccine 
(or placebo) at the first three vaccination visits.  You will need to wear the patch for 6 hours ±2 
hours (range 4-8 hours) after application. After that time period, you will remove the patch and 
record the time on the diary card. 
After the experimental vaccine injection, the clinic staff will observe you for 30-60 minutes and 
you will have your vital signs checked before leaving the clinic. You will write down your 
temperature and any symptoms you might have in a Diary Card while in the clinic, 30-60 
minutes after the vaccination. You will be asked to complete a Diary Card at home about 6 hours 
after the injection and then daily for the 7 days after the experimental vaccination. The diary is 
for you to record your temperature and symptoms and look at the injection site each day and we 
will explain to you how to do this. You will be given a thermometer to take your temperature and 
ruler to measure any injection reactions as well as instructions. The diary card is very important 
for this research and needs to be returned to the study staff at the next visit. When you return to 
the clinic, if there is missing information on your diary or if the diary is lost, you will be asked to 
fill in the blanks to the best of your recollection, but you will not be able to fill in your 
temperature or measurements.  
The clinic staff will contact you 24 to 48 hours after each vaccination to see how you feel. You 
will be asked to report any symptoms to the study doctor or nurse right away, and come to the 
study clinic for an examination, if necessary. You will also need to come to the clinic for any 
problem, which the nurse or doctor thinks should be checked by exam, blood, urine or other 
medical test. These visits may be in addition to your already planned study visits.  If you are 
unable to be contacted by telephone, study staff will visit you at home with a home visit.    
If you experience serious reactions, the study doctor may decide that you should not receive any 
further experimental vaccine injections. However, you may be asked to continue to be a part of 
the study and to return for follow-up study visits and tests.  A photograph may be helpful to 
document an unusual or unexpected finding after the experimental vaccination is given. Also, if 
you undergo lymph node biopsy, the study doctor may take pictures of the biopsy site 
immediately after the procedure and again about 6 months later to document how well your 


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biopsy site healed and for possible use as educational material for other participants who undergo 
the same procedure.  
You will be asked to sign an additional consent form for photography if pictures will be taken. 
No one will be able to determine your identity from these pictures. 
Follow up visits:  
You will be checked for any new symptoms since your last visit. You will be asked how you are 
feeling and if you are taking any medicines. You will be asked to give blood samples for 
laboratory tests to monitor your health, test for HIV (at certain visits, see your participant 
schedule), and for research purposes.  
All clinic visits require a blood draw and the amount of blood drawn will vary from about 18.0 
mL (a little more than 1 Tablespoon) to about 171 mL (11 1/2 Tablespoons) depending on the 
visit. 
Please refer to the participant visit schedule given to you to keep track of what can be expected 
from you at each visit. 
4. 
What are the experimental vaccines? 
There are two experimental HIV vaccines tested in this study: the Env DNA vaccine and the 
gp145 protein vaccine. Each is given with different adjuvants which may make the vaccine more 
effective. The Env DNA vaccine has been tested in clinical trials and is relatively well tolerated 
by the body. The HIV gp145 protein vaccine to be tested in this trial will be the first time this 
vaccine is used in humans, but very similar products have also been tested in humans and are 
generally well tolerated.  
There are three adjuvants used in this study in different combinations.  
1. Rehydragel, or an aluminum hydroxide-based substance is approved for use and has been 
in-use in at least ten FDA licensed vaccines in the US and 146 vaccines worldwide.   
2. ALF43 will be tested for the first time in humans and we are not certain if it is safe – we 
do know that an earlier form of ALF43 called L(MPLA) has been shown to be safe in 
several studies.   
3. dmLT, another adjuvant, is given with a needle-free skin patch and has been used in 
many studies with no notable side-effects.  
 
These adjuvants are mixed with the experimental vaccines and injected in the muscle; one of the 
adjuvants (dmLT) is applied to the skin where the injection is given as a skin patch and covered 
with a bandage.  This is the first time this method will be used in humans.   
It is important to remember that the HIV vaccines do NOT contain the entire HIV virus itself and 
cannot cause HIV infection or Acquired Immune Deficiency Syndrome (AIDS).  
The following experimental vaccines will be used in this study, if you are assigned for groups 1-
7, the injection you receive will contain only one experimental vaccine.  If you are in group 7, 


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the injection will contain both. We hope to understand if different adjuvant combinations are 
safe, tolerable and how they stimulate your immune system.  
 
Experimental vaccines 
• Env-C Plasmid DNA (HIV-1 gp120 (93MW965.26) DNA)  
• HIV Env gp145 C.6980 protein  
Adjuvants 
• ALF43 Army Liposome Formulation with Monophosphoryl Lipid A (MPLA) and 
43% Cholesterol (referred to as ALF43) 
• Rehydragel® (Aluminum Hydroxide) 
• E. coli double mutant heat labile toxin (dmLT) 
This research study is a double-blind study, which means that neither you nor the research team 
will know whether you are receiving the research study vaccines or a placebo.  In the event of an 
emergency, there is a way to find out which one you are receiving. 
Each of the 7 groups will have 15 participants that receive the experimental vaccines and 3 
participants who will receive the placebo.   
If you decide to participate in this study, you will be assigned randomly to one of seven (7) 
groups in the study and to receive either placebo (an inactive substance that does not contain the 
experimental vaccine—like salt-water injections) or a vaccine.  
Enrollment into the groups will be done in a step-by-step way for safety reasons.  Group 1 will 
receive a vaccine combination that has been given before and doesn’t need a pause for safety 
reasons, while the vaccine combinations in Groups 2-7 are new and have not been tested before.  
Therefore, the Groups will proceed in the following manner.  All of Group 1 will enroll and 
receive their first vaccine.   Groups 2-7 will then start enrolling until 4 participants from each 
group (24 total) have received the first vaccine.  Enrollment for Groups 2-7 will then stop for 
about a week to allow the researchers to look at the data and see if it is safe to give the remaining 
participants their vaccines.  
 
There will also be a second pause a little later in the study once all of Group 1 and those first 24 
participants in Groups 2-7 receive their 1st boost (Dose 4 at Week 20).  Again, this is for safety 
reasons. This second pause will only stop the Week 20 boost vaccinations for the remaining 
participants in Groups 2-7. Earlier vaccinations (Doses 1-3) will not stop.  This pause will last 
for about a week to allow the researchers to look at the data and see if it is safe to give the 
remaining participants their Week 20 boost. 
 
None of experimental HIV vaccine combination groups have been shown that they work to 
protect against HIV infection. Also, there is also a possibility that you may be assigned to receive 
the inactive placebo. 


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A schedule of the assignments for each group is below: 
Group Prime at weeks 0, 4, 12 
Boost at weeks 20, 32, 56 
1 
Env-C Plasmid DNA IM 
HIV Env gp145 C.6980 protein 
/Rehydragel® IM 
2 
Env-C Plasmid DNA IM 
HIV Env gp145 C.6980 protein 
/ALF43/Rehydragel® IM 
3 
Env-C Plasmid DNA IM + dmLT TCI 
HIV Env gp145 C.6980 protein 
/Rehydragel® IM 
4 
Env-C Plasmid DNA IM + dmLT TCI 
HIV Env gp145 C.6980 protein 
/ALF43/Rehydragel® IM 
5 
Env-C Plasmid DNA/ALF43 IM 
HIV Env gp145 C.6980 protein 
/Rehydragel® IM 
6 
Env-C Plasmid DNA/ALF43 IM 
HIV Env gp145 C.6980 protein 
/ALF43/Rehydragel® IM 
7 
Env-C Plasmid DNA/gp145/ALF43 IM 
Env-C Plasmid DNA/HIV Env gp145 
C.6980 protein /ALF43/Rehydragel® IM 
IM= intramuscular (injected in the muscle), TCI = transcutaneous application (applied to the 
skin) 
 
5. 
What are my responsibilities during this study? 
If you take part in this study, you will be asked to: 
• Provide complete and accurate information about your medical history, medicine use, 
and any symptoms or illnesses you have during the study. 
• Agree to not participate in any other research study or donate blood during your 
participation in the study.  
• Agree to have photo or fingerprint taken for identification purposes 
• Follow the study staff’s instructions. 
• Attend all appointments and be available for telephone calls from the study staff. If 
you cannot keep an appointment, contact the study clinic immediately to reschedule. 
• Agree to home visits. The study staff will take you home after the first vaccination in 
order to adequately describe your home location to allow for home visits in future 
should the study staff be unable to contact you by telephone.   
• Female participants must use an adequate birth control method for 45 days prior to 
the first injection or patch and for at least 90 days after the final injection, as it is 
stated in the protocol. 
• If female and able to become pregnant, avoid pregnancy but immediately inform the 
study doctor or staff if you do become pregnant during the study. If you are found to 
be pregnant at any study visit after the screening visit you will stop receiving study 
injections, but you will continue to be followed-up for the remainder of the study and 


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your pregnancy will be followed until your baby is born Blood will be drawn only for 
safety testing.  
• Inform the study doctor or staff of any health problems, side effects, visits to another 
doctor or hospital and any changes in your plans or ability to participate in the study. 
 
6. 
How long will I be in this study?  
If you decide to join, you will be in this study for about 105 weeks (26 months).   
You will be asked to complete at least 26 clinic visits.  Please note that you may be asked to 
come to the clinic for an unplanned visit if you experience side effects that are of concern.  
Additionally, you will be contacted by phone, once per week for three weeks, to discuss any 
changes you may have experienced after the first 105 weeks of being in the study.  
You will be vaccinated six (6) times (at weeks 0, 4, 12, 20, 32, 56) during this study.  The 
vaccinations will be given by injection, like most approved vaccines, in the muscle of your upper 
arm. The first vaccination visit could take up to 6 hours, but the other vaccination visits take 
about 4 hours each. Most other follow-up clinic visits will usually take about 2 hours.  
7. 
How many participants will be in this study? 
126 healthy men and women, 18-40 years old will be in this study.  We think that one out of 
every four people screened will be eligible which is about 504 potential participants.  
8. 
What possible risks can I expect from participating in this study? 
Blood draws: 
In this study, study staff will take some blood from you at every visit.  The total amount of blood 
collected over 26 months is about 128 TBSP. Blood draws can, at times, cause bruising, pain, or 
fainting. They rarely can cause an infection.  Blood is drawn by qualified staff that have been 
trained in drawing blood.  
Vaccines and adjuvants: 
This is an early human research study to examine the safety of these vaccines and adjuvants.  
You are one of the first humans to receive this combination of vaccines and adjuvants.  As a 
result, not all the side effects are known. All vaccines can cause fever, chills, rashes, pains, 
nausea, headache, dizziness, and sleepiness. Most people are still able to do their daily activities 
after getting a vaccine.  Rarely do they need to go to the doctor.  Frequently, vaccines cause pain 
and swelling where you get the injection.  These local reactions are usually mild.   
People who have received the DNA vaccine that will be used in this study have reported a 
delayed allergic reaction (appearing 24 to 48 hours after vaccination) at the site of injection.  
Another common reaction seen was a “recall” reaction.  This reaction can range from redness to 
swelling, rash, and pain, which appears at the site of a previous injection, typically 36 to 72 
hours after the most recent injection.  Reactions that occurred after DNA vaccine was injected 
were described as mild.  Reactions that occurred after protein was injected ranged from mild to 
severe. 


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You may take over the counter medicines to help with any discomfort you may have after the 
experimental vaccinations, but please report any use of these medicines to the clinic staff.  
Rarely, a vaccine causes an allergic reaction.  This reaction can be a rash, hives, or difficulty 
breathing.  You should tell the study staff if you have ever had a bad reaction to an injection or a 
vaccine.  Allergic reactions can be life-threatening. If needed, participants will be transferred to 
the Unilever Hospital for further management. 
An adjuvant is a liquid substance added to vaccines that can help to make the vaccine more 
effective by improving the immune response or causing the immune response to last longer than 
without the adjuvant. The adjuvants that will be mixed with the experimental vaccines have been 
used in other research studies and the most common reactions at the injection site are pain or 
tenderness, redness and a bump under the skin. Other common reactions are not feeling well in 
general, muscle aches, headache, fever, and nausea. These reactions have been reported to be 
mild to moderate.   
The body’s immune system protects the body from infections.  Sometimes, a person’s immune 
system attacks the body instead, causing an “autoimmune disease”.  A vaccine can cause this 
type of disease or make it worse, but this is very rare. 
Pregnancy and breastfeeding:  
Researchers do not know if the vaccines may harm unborn babies.  You should not become 
pregnant during this study. If you are having sex that can make you pregnant, you should use 
birth control.  Researchers will talk with you about acceptable birth control methods.  You 
should use them from beginning 45 days prior to the first vaccination and continuing through 90 
days after the last study injection. Researchers will test you for pregnancy throughout the study. 
Adequate birth control is defined as follows: Oral contraceptives, injection or implant, surgery 
(hysterectomy or tube tie), condoms with spermicide, diaphragms, intrauterine device (IUD), 
vasectomy in a monogamous partner, or abstinence. 
 
If you become pregnant during this study, you will stop getting the study injections but will 
remain in the study for observation which will include small blood draws but only to check your 
heath.  Study staff will help you find out about available care for you and your baby.  This study 
will not pay for this care.  Knowing the results of your pregnancy is important, so study staff 
may ask you to come back for visits or may call you.  Additionally, you should not breastfeed 
while in this study because researchers do not know if the vaccines may pass through breast-milk 
and may harm your baby.  The study team will follow your pregnancy until your baby is born. 
Transcutaneous immunization skin patch (TCI):   
TCI is a needle-free skin patch applied to the skin like a bandage that, by itself, has been found 
to be safe and well tolerated.  Common reactions to TCI are redness and bumps where the patch 
is applied to the skin, and changes in skin pigmentation at the site of patch application. When 
combined with the experimental vaccine, TCI administration side effects may include itching, 
mild redness or rash, and changes in pigmentation at the site of patch application.  If change in 
pigmentation occurs, it could be permanent.  


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VISP: 
The vaccines may cause “vaccine-induced sero-positivity” or “VISP”.  So, if you are in the 
group that receives the experimental vaccine and not the placebo, you may test HIV positive 
when you really do not have HIV. This clinic’s HIV test can tell the difference between real HIV 
infection and VISP. For this reason, you should avoid all HIV testing not done at this clinic.  
You will be tested for HIV regularly during this study.  After this, if you would like HIV testing, 
we encourage that you return to this clinic for testing.  Researchers do not know how long you 
may have VISP.  At your request, you will be provided with a letter explaining your participation 
in the study and the possibility of testing positive for HIV antibody.  If you have problems 
because of VISP, with your written permission, the study staff will assist you with any unfair 
treatment you may experience by being in this study. This includes talking to insurance 
companies, employers, and others to verify your study participation or advocate on your behalf.  
Also, if you become pregnant and have the baby while you have VISP, your baby may have 
VISP too.  This clinic’s HIV test can tell the difference between real HIV infection and VISP in 
your baby as well.  
If you have VISP, you cannot donate blood and you must not donate blood during your 
participation in this research study for other reasons as well. If you wish to donate blood after 
you have completed participation in this study, blood donation options will be explained at the 
final study visit, however you may be excluded in the future from donating blood when you 
reveal that you participated in an HIV vaccine study.  For the same reason, you may also be 
excluded from participation in other research studies.  
Social issues: 
You may face personal problems because of being in this study.  Family, friends, and others may 
worry, get upset, or treat you unfairly.  People may think that you have HIV or are likely to get 
it. You could lose your job because your employer thinks that you have HIV, or because you 
take too much time away from work to be in this study, but it is unlikely.  
You may feel embarrassed when answering personal questions about sex or having a physical 
exam.  You may feel anxious when waiting for your HIV test results. If you have these feelings, 
please tell the study staff so that they can find a way to help you. 
Researchers and study staff try hard to protect your privacy.  They also have a duty to maintain 
your privacy.  But there is a risk that others, including your partner, may find out that you are 
participating in this study.  So, they may treat you badly or discriminate against you.  Your 
partner may decide to insult you, leave you, or hit you.  Your partner may stop paying for things.  
Another social risk is that someone may use your personal information in a bad way.  For 
example, someone finds out your test results and shares them with others.  You could then have 
problems getting or keeping a job.  You may no longer have your family’s or your community’s 
support.  These situations may cause you stress and embarrassment.  Researchers have ways to 
reduce these social risks. Some of these ways include limiting access to your study records, 
having your study visits in private, and using codes to identify you and your samples.  If you 
have any of these problems, please talk to the study staff, so that they can try to help you. 
Genetic testing:  


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The greatest risk associated with genetic testing is to your privacy. Genetic testing is described 
below in section 10. 
9. 
What possible benefits can I expect from participating in this study? 
You will not directly benefit from participating in this study.  The results of this study will be 
shared with researchers from around the world and could play a role in future HIV vaccine 
development which may be beneficial in the future for others.  These experimental HIV vaccines 
have not shown that they work to protect against HIV infection. Also, there is also a possibility 
that you may be assigned to receive the inactive placebo.  
Some small benefits for study participants may include no cost detailed medical, physical and 
laboratory examinations and potential care for minor ailments.  
10. 
What will happen to my samples and data?  
HIV vaccine studies are done to learn how experimental vaccines affect your immune system 
and how your body responds. To better understand this, at each visit, the study doctors take 
blood samples to assess your heath and for research testing.  Clinical information that may be 
beneficial to your health will be shared with you but your results from the research testing will 
not be shared with you. You may be asked to give more blood, if needed, to assess your health. 
Genetic testing may be conducted on your samples during this study and in the future.  For 
example, researchers may do “genetic variations” research. They may look at genes that affect 
how you fight infections.  Your genes are passed to you from your birth parents. Genes are the 
basic “instruction book” for the cells that make up our bodies. The differences in people’s genes 
can help explain why some people get a disease while others do not. We will not notify you of 
the results of any genetic test. The genetic research tests we plan to conduct are not currently 
used in medical practice.  The results of such tests have not been approved for use in making 
health care decisions and the results will not be shared with you. To protect your identity, your 
genetic testing results will not be linked to your name and will not independently identify you as 
an individual.  The research for this study will not include mapping of all your genes (called 
“whole genome sequencing”). 
Some of the blood samples will be shipped to the USA and or Thailand for tests are not available 
at this site.  The blood that is left over will be stored at the KEMRI/USAMRD-A Kericho CRC 
lab for use in the future.  We will share study information and or samples to research 
collaborators outside of KEMRI/USAMRD-A and to research collaborators outside of Kenya 
without asking for your permission and there is no time limit on how long your data and samples 
will be stored for future use.  Documents, (including this form) notes from your visits, and 
photographs, if any, will be stored securely and then destroyed by authorized individuals when 
these records are no longer needed.  You have the option to allow your specimens to be used for 
future research and you can also choose to allow or decline genetic research at the end of this 
form. If you agree now and decide later that you do not want us to use your samples for future 
research, please tell us. We will ask the storage facility to destroy any remaining samples that 
still have your study ID on them so that they cannot be used for future research.  Samples that are 
“deidentified”, meaning they do not have your study ID on them, will not be withdrawn from 
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The overall results and findings from this study will not be shared with you.  
Please see section 12 that explains the methods we use to protect your privacy.  
11. 
What other choices do I have? 
If you choose not to participate in this study: 
• You could choose to participate in other studies  
• You may choose to get HIV counseling and testing outside this study  
If you would like more information about the risks and benefits of each one of these choices, feel 
free to talk to the study staff.  You can also discuss these options with your doctor.  Regardless 
of your choice, any care that you get at this clinic outside of this study will not change. 
12. 
How will researchers protect the privacy of my information?   
You will be identified by a fingerprint identification system (with/without a picture) on a 
computer.  We will be storing the information generated by your fingerprint along with your 
name and address in a secure database for the purpose of identifying participants. Only 
authorized study staff can access this information. Your fingerprint, photograph, name or other 
identifier will not be attached to any of your samples or test results or other study information, 
now or in the future. 
Researchers have protections in place to maintain your privacy.  They keep your study records in 
a secure place.  They do not use your name in publications, meetings, or stored samples.  They 
use a code to identify you and your samples.  They do not share any information that could 
identify you. Complete confidentiality cannot be promised, but every effort will be made to keep 
the records as confidential as possible within the limits of the law. All data and medical 
information obtained about you as an individual will be considered important and held in 
confidence.  
The Principal Investigator, Dr. Josphat Kosgei, is in charge of the research records of your 
participation in this study. All study participants will receive participant identification numbers 
or study ID known only to the study team at the clinic and used to ensure the confidentiality of 
your information. Your samples will be labeled with your participant identification number 
(study ID) and will not identify you by name. A key to the code connects your name to your 
study information and samples. The study doctor or authorized study staff will keep the key to 
the code in a locked cabinet in a restricted-access room here at KEMRI/USAMRD-A and will 
not share it with our research collaborators. No one outside of KEMRI/USAMRD-A will know 
which participant the samples came from. Before any data or specimens are sent to research 
collaborators, approvals will be obtained from the WRAIR IRB and KEMRI SERU.  
The study records will be stored at the KEMRI/USAMRD-A triple-locked filing room for the 
period when the study is active, and thereafter transferred to the site’s archive for long term 
storage.  When your records and samples are no longer needed, they will be destroyed.  


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There are several organizations watching over this study.  They want to make sure that 
researchers are protecting your rights and keeping you safe.  They also want to see if researchers 
follow the approved study protocol. People from these organizations may review your records. 
These people have a duty to maintain your privacy.  Some of these organizations are: 
KEMRI SERU, Kenya PPB, the Kenya Ministry of Health, USAMRDC ORP, HRPO, the 
NIAID, the NIAID Office of Human Research Protections (OHRP), the US FDA, WRAIR, the 
people who work for these organizations, and other local, US, US DoD, or international 
regulatory agencies as part of their responsibilities for ensuring the protection of research 
participants. All the above representatives are bound by rules of confidentiality not to reveal your 
identity to others.  By signing this consent form, you are authorizing this access. 
Throughout the study, investigators will be collecting data related to the safety of participating in 
this study and receiving study products.  That safety data will be stripped of any personal 
identifiers and will be added to a database in order to help researchers learn more about potential 
issues that may affect safety across multiple studies.  Data collected for the safety database will 
include the following: study title, information on the safety event, your gender, age, and location. 
Additionally, it is the policy of the USAMRDC that data sheets are to be completed on all study 
participants participating in research for entry into this Command’s Volunteer Registry Data 
Base. The information to be entered into this confidential database includes your name, date of 
birth, address, study title and dates. The intent of the database is two-fold: first, to readily answer 
questions concerning an individual’s participation in research sponsored by USAMRDC; and 
second, to ensure that the USAMRDC can exercise its obligation to ensure research study 
participants are adequately warned (duty to warn) of risks and to provide new information as it 
becomes available. The information will be stored at USAMRDC for a minimum of 75 years. 
13. 
Will I have to pay anything to participate in this study? 
You will not have to pay for any study lab tests, procedures, or exams.  Your insurance provider 
will not have to pay either. You will not have to pay for any of the study procedures.  
14. 
Will I receive any payment for my participation in this study? 
You will receive reimbursement for your transportation costs, time, and lost wages that may 
result from sick days taken after the procedure. You will receive reimbursement for the main 
study even if you don’t take part in any of the optional procedures.  There is no other 
compensation available for your participation in this research study; however, you should also 
understand that signing this consent form is not a waiver or release of your legal rights. 
Other than medical treatment that may be provided, there is no other reimbursement available for 
your taking part in this research. If you choose to end your study participation early, you will 
receive reimbursement only for the portion of the study that you have completed. 
We may use your samples and information to develop a new product or medical test to be sold.   
The Sponsor and researchers may benefit if this happens. There are no plans to compensate you 
if your samples are used for this purpose. 


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Reimbursement amounts are as follows: 
 
• Study visits:   
 
1000 Ksh 
• Unscheduled visits:   
Up to 500 Ksh, at the discretion of the study investigator 
• Mucosal collections:   
1000 Ksh per each collection 
• Lymph node biopsy:  
5000 Ksh 
• Transportation:  
 
Up to 3000 Ksh, at the discretion of the study investigator 
The clinic staff will provide compensation to participants in cash at the clinic site upon 
completion of the visit study procedures. 
15. 
Can I change my mind about participating in this study? 
Yes, you can change your mind at any time.  Your participation in this study is completely 
voluntary.  Tell the study staff if you are thinking about leaving or have decided to leave this 
study.  Again, any care that you get at this clinic outside of this study will not change. 
Study staff may want you to do some follow up visits and testing before you leave this study.  
16. 
Can researchers take me off this study early? 
Yes, researchers can take you off this study at any time: 
 
• If they believe it is the best thing for you 
• If you do not follow the study requirements 
• If one of the groups watching over the study stops it  
• If you become pregnant 
• If you have a serious side effect that is related to the study vaccine. 
• If you become HIV positive 
• If you become incarcerated 
• If you have a medical problem where continuing to be in the study would be harmful to you. 
If you become pregnant or ill and can no longer participate in the study, the researchers may ask 
you to return for follow up visits to assess your health. 
17. 
What happens if I become HIV infected during this study? 
Researchers do not know how the experimental vaccines in this study may affect your risk of 
getting HIV. If you get HIV, they do not know if the vaccines would affect how bad your HIV 
infection will be.  Also, they do not know if the vaccines would change how you may respond to 
other HIV vaccines in the future.  Currently, there is no vaccine for HIV.  If you become HIV 
infected during this study, study staff will tell about any available care and you will not be 
allowed to remain in the study. Study staff will counsel you about your HIV infection.  They will 
also tell you how to lower the risks of giving HIV to others. 


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18. 
What are my rights and who should I contact if I have questions? 
You have the right to leave this study at any time and for any reason.  The study staff will 
continue to treat you the same no matter what you decide.  You will not give up your legal rights 
by signing this informed consent form.  You also have the right to know about any new 
information from this study or other studies.  This information may affect your health, welfare, 
or decision to stay in this study. 
If you have questions about your rights as a study participant, contact: 
 
Kenya Medical 
Research Institute 
(KEMRI) 
 
Office:  
020 27541 or 
0722205901 or 
0733400003 
Mail:  
Kenya Medical Research Institute (KEMRI) 
SERU P.O. BOX 54840-00200 Nairobi 
 
19. 
Who should I contact if I think that I am hurt because of my 
participation in this study? 
If you get sick or injured due to participation in this study, you will receive appropriate medical 
treatment and care as provided with costs for such treatment covered by a limited fund and a 
clinical trials medical insurance policy. While we anticipate the combination of the set-aside 
fund and the insurance policy is enough to pay for the cost of any injury associated with this 
study, there is a limit to the amount of coverage available.  If the limit is exceeded, you may have 
to pay non-covered costs. 
KEMRI/USAMRD-A will pay costs up to the limit from dedicated funds or through the clinical 
study insurance. However, you will not get any other compensation because of an injury directly 
related to your participation in this study.  KEMRI, the US Army, or US NIH is not able to 
reimburse you for these treatment expenses.  The United States Department of Defense will not 
pay for research-related injuries. 
If you think you are hurt because of your participation in this study, please tell Dr. Kosgei or 
Rael Bor.  You can do it in person or call the numbers provided at the beginning of this form. 
20. 
How do I confirm my decision to be in this study? 
My signature below confirms: 
• that I voluntarily decided to participate in this study 
• that I had the opportunity to read this form  
• that this form was explained to me 
• that I had the opportunity to ask questions  
• that I had the opportunity to discuss my study participation with others 
 


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If there is any portion of this document that you do not understand, ask the study staff before 
signing the form.  Signing this form means that you consent to participate in this research, at this 
time.  A signed and dated copy of this document will be given to you. 
21. 
Your choices about how your biological samples may be used: 
Future Research: 
Researchers may store and use my biological samples and data to find new ways to detect, 
treat, prevent, and cure health problems. 
____ Yes, I agree. 
     initials 
____ No, I do not agree. 
     initials 
 
Genetic Testing: 
Researchers may store and use my biological samples and data now and in future research to 
learn about how genes play a part in diseases.  
____ Yes, I agree. 
     initials 
____ No, I do not agree. 
      initials 
Additional information about the trial is available at http://www.ClinicalTrials.gov website. 
 
SIGNATURE OF PARTICIPANT  
 
 
________________________________________ 
Printed Name of Participant 
 
 
________________________________________  
______________ 
Signature of Participant 
 
 
 
 
 
Date 
 
SIGNATURE OF INDIVIDUAL ADMINISTERING CONSENT 
(Can only be signed by an investigator or staff approved to administer consent) 
 
_______________________________________ 
Printed Name of Administering Individual 
 
________________________________________  
______________ 
Signature of Administering Individual 
 
 
 
Date 


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OPTIONAL PROCEDURES CONSENT 


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Kenya Medical Research Institute (KEMRI)  
United States Army Medical Research Directorate-Africa (USAMRD-A) 
In Collaboration with 
US Military HIV Research Program and the 
US Department of Defense (DoD) 
 
RV460/WRAIR #2672 Informed Consent Form for Optional Procedures 
 
Protocol Title: 
A Randomized, Double-Blind Phase 1 Trial to Evaluate the Safety and 
Immunogenicity of Priming with Env-C Plasmid DNA Vaccine Alone, 
with Different Adjuvants, or with an Adjuvanted HIV Env gp145 C.6980 
Protein Vaccine and Boosting with the Adjuvanted HIV Env gp145 
C.6980 Protein Vaccine with or without the Env -C Plasmid DNA Vaccine 
in Healthy HIV Uninfected Adults in Kenya 
Sponsor: 
National Institute of Allergy and Infectious Diseases (NIAID), Division 
of AIDS (DAIDS) Bethesda, Maryland US  
 
Funding: 
United States Army Medical Research Acquisition Activity  
U.S. Military HIV Research Program   
Henry M. Jackson Foundation for the Advancement of Military Medicine  
 
Site: 
 
Kenya Medical Research Institute (KEMRI) US Army Medical Research 
Directorate-Africa (USAMRD-A), Kericho, Kenya 
 
Introduction 
This consent form is for you to learn about and to help you decide to give permission for certain 
optional procedures as part of this study. You do not have to agree to any of these procedures 
and you can still participate in the main study.  
 
The 2 optional procedures are: 
 
• Collection of rectal and genital secretions, also called mucosal secretions 
• Lymph node biopsy 
 
Please refer to the participant visit schedule given to you to keep track of what can be 
expected from you at each visit. 
 


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Key Information for You to Consider 
Voluntary Consent. You are being asked to volunteer for a research study.  It is up to you 
whether you choose to participate or not.  There are no penalties and you will not lose 
anything if you decide not to join or if after you join, you decide to quit.   
Purpose. We are doing this research to test a vaccine for HIV and vaccine additives called 
adjuvants that can help the vaccine be more effective.  The tissue samples requested in this 
optional part of the study will help us learn about how your immune system responds in 
tissue other than blood. 
Duration. Mucosal collections will occur at 9 visits (Visits 1,7, 11, 15, 18, 22, 23, 24, and 
25) over the course of study.  Lymph node biopsies will be performed at weeks 14 and 
week 58. 
Procedures and Activities. Collection of mucosal secretions - cervicovaginal secretions, 
semen or rectal secretions at up to 9 clinic visits and up to 2 groin lymph node biopsies.  
Risks. Most studies have some possible harms that could happen to you if you join.   
It is possible that these optional procedures could cause an unpleasant or serious effect, for 
example:  Collection of mucosal secretions may be uncomfortable and embarrassing.  
There is a rare possibility that women that use the Softcup develop a serious illness called 
toxic shock syndrome (TSS).  
The lymph node biopsy could leave a scar, cause bleeding or an infection. You should 
know that there is a chance that there is a small chance of developing a large scar (keloid) 
or temporary or permanent loss of feeling around the biopsy site.  
Benefits. You will not directly benefit from participating in this study.  The results of this 
study will be shared with researchers from around the world and could play a role in future 
HIV vaccine development which may be beneficial in the future for others.   
Alternatives. Participation is voluntary, and the only alternative is to not participate. 
 
Please contact one of the below if you have any questions concerning the study or if you have 
any other questions or concerns.  
If you have questions about this study, contact: 
 
Dr. Josphat Kosgei, 
MBCHB, MSc  
 
Office: 
(0)5220 36302 
 
Mobile:  
(0)729 110 122 
 
Staff:  
(0) 5220) 36000/100 
 
If you have any symptoms that you think may be related to this study, contact: 
 
Rael Bor, BSc 
 
Office: 
(0)5220 36329 
 
Mobile:  
(0) 729110121 
 
Staff:  
(0) 5220) 36000/100 


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1. 
Why is this research being done? 
The main purpose of this study is to find out if the experimental vaccines with adjuvants used in 
this study cause side effects, whether humans respond (develop immune responses) to the 
experimental vaccines, and how long the effects of the experimental vaccines last. Some results 
from other studies have suggested that the immune cells in your secretions might play a role in a 
person’s chances or getting HIV. The tissue samples requested in this optional part of the study 
will help us learn about how your immune system responds in tissue other than blood.  
 
2. 
What possible benefits can I expect from participating in this part of the 
study? 
You will not directly benefit from participating in this study.  The results of this study will be 
shared with researchers from around the world and could play a role in future HIV vaccine 
development which may be beneficial in the future for others.   
 
3. 
Who can participate in this part of the study?  
Optional procedures are open to all the participants that are enrolled in the main study and are 
eligible and willing to provide these additional samples. Not all participants will be eligible for 
this part of the study.  There may be reasons why you would not be able to participate in the 
optional procedures. Your eligibility will be decided by the study doctor after reviewing your 
medical history and physical exam. 
4. 
What should I know about the different optional procedures? 
We would like you to know the following: 
 
• You may not undergo these optional procedures if you become pregnant because these 
may cause unforeseeable risk to you or your baby. 
• If you undergo any of these optional procedures and there is evidence of an abnormal 
finding, you will be referred for diagnosis and care. You will not be informed about any 
research results that come from your samples.  
 
Collection of Genital and Rectal Secretions 
1. 
Why is the collection of mucosal secretions done? 
One of the ways that people become infected with HIV is through contact with genital secretions. 
HIV virus can be spread through genital secretions.  Researchers do not know much about what 
happens in the genital tract after an HIV vaccination is given and we hope to learn about 
improving protection from HIV in the genital tract.  


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2. 
How is the collection of genital and rectal secretions done? 
Cervicovaginal Secretion Collection (women) 
 
You must refrain from vaginal intercourse, douching or inserting any object into your vagina for 
72 hours prior to the collection.  If you are menstruating (bleeding), the vaginal sampling will be 
done at another time.  Also, the collection will be delayed if you have symptoms of active 
inflammation or infection in the vagina or cervix.  If you become pregnant during the study, you 
cannot continue participation in this part of the study.  
 
At each sample collection visit, you will be asked a series of questions to be sure that you are 
eligible to provide the specimens.  Additionally, you cannot use the Softcup during the six-week 
period immediately after childbirth, miscarriage, or termination of pregnancy. 
 
A trained nurse or doctor will show you how to insert a soft plastic cup (Softcup) into your 
vagina to collect the vaginal secretions.  The Instead Softcup is approved by the United States 
Food and Drug Administration (FDA) as a feminine hygiene alternative to pads and tampons for 
use by women during menstruation.  The Softcup cannot be used to prevent pregnancy and does 
not protect you from getting a sexually transmitted infection (STI). 
 
A nurse or doctor can insert the cup for you before your appointment or you may insert it 
yourself. After you learn about how to use the cup, you may choose to insert the cervical cup 
yourself at home before you come to the clinic and remove it when you come to the clinic for 
your study visit. The cup should remain in the vagina for at least four hours, but not more than 
12 hours to be able to obtain enough secretions.  To remove the cup, you will be given a plastic 
container and be instructed to go alone into a private room in the clinic, remove the cup, place it 
in the container and close the container.   
 
You can choose not to provide the cervicovaginal secretion sample and still participate in rectal 
secretion collection and lymph node biopsy described below. 
 
Semen Collection (men) 
 
You must refrain from masturbation or ejaculation for 72 hours prior to the collection. At each 
sample collection visit, researchers will provide a private room for you to provide the semen 
sample.  In this room, you will ejaculate into a sterile container.  
 
You can choose not to provide the semen sample and still participate in rectal secretion 
collection described below. 
Rectal Secretion Collection (women and men) 
 
You must refrain from any kind of sexual activity or inserting anything into your rectum for 72 
hours prior to collection.  You will not be allowed to participate in the rectal secretion collection 
part of this study if you have a gastrointestinal disorder or an illness that may result in increased 


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inflammation including autoimmune diseases such as rheumatoid arthritis, systemic lupus 
erythematosus, or psoriasis. 
 
A nurse or doctor who has been trained to do an anal examination will examine you in a private 
room.  The nurse or doctor will insert an instrument into the anus to inspect the tissue in the 
lower rectum and use a sponge to collect secretions in the lower rectum.  
You can choose not to provide rectal secretions and still participate in the vaginal secretion 
(women) and semen (men) collection.  
3. 
How often is the collection of mucosal secretions done? 
You will be asked to provide a sample nine times; at visits 1,7,11, 15, 18, 22, 23, 24, and 25.  
You can choose which samples you wish to provide at each visit.  Please see the schedule 
provided by the study staff. 
4. 
What are the risks of the collection of mucosal (cervicovaginal, rectal, or 
semen) secretions? 
Both men and women may feel shy about exposing your private areas during the examination. 
Nurses and doctors performing this procedure have been specially trained and will conduct the 
examinations in a private area.  
 
For women, inserting the Softcup into the vagina may cause discomfort and slight irritation 
similar to inserting a tampon but it should not cause any pain.  There is no evidence of Softcup 
sampling contributing to risk of HIV or other sexually transmitted infection.  Squirting fluid and 
swabbing in the vagina may cause some irritation. 
 
If you are a woman and you have a history of toxic shock syndrome (TSS), you cannot 
participate in vaginal secretion collection.  TSS is a rare but serious disease that is believed to be 
caused by a bacterial toxin and is associated with keeping a tampon in the vagina for too long 
without changing it.  Symptoms of TSS include a sudden high fever, vomiting, diarrhea, a rash 
that looks like sunburn, dizziness, fainting or near fainting, and muscle aches.  TSS can quickly 
become a serious illness that can be fatal.  If you have any of these signs and you are using the 
Softcup, remove it and immediately contact your physician for medical care at once.  You must 
not use the Softcup for more than 12 hours.  
 
Men might feel uncomfortable giving semen samples.   
For both women and men, inserting an instrument into the anus may be uncomfortable but it 
should not cause pain.  Squirting fluid and swabbing in the anus could cause some irritation. 
 
Lymph Node Biopsy 
1. 
What is a lymph node? 
Lymph nodes are small nodules that are a part of your immune system and can be found behind 
the ears, in the neck, in the armpit, and in the groin.  Lymph nodes are responsible for producing 
some white blood (immune) cells called lymphocytes as well as filtering the fluid that carries 


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them around in the body.  They usually swell when you have an infection nearby (e.g. a wound 
on the leg can cause the lymph node in your groin to swell). 
2. 
Why is lymph node biopsy done? 
Two of the main types of cell that are important in the body's immune system, the T cell and the 
B cell, are found in large numbers within your lymph nodes. In the future, to try to develop better 
treatments for and vaccinations against HIV, it is important for us first to understand the 
interactions between these cells, their roles in immunity and how these are affected by the 
experimental vaccine in this study. 
3. 
How is lymph node biopsy done? 
A surgeon will perform the lymph node biopsy using local anesthetic. This means you will be 
awake, but the biopsy area will be numb. Please let us know if you are allergic to any 
medications. The surgeon will biopsy a lymph node in the groin area because this is the safest 
location with the smallest risk of problems. The surgeon will clean your groin with an antiseptic 
solution and then make a small cut in the groin (about 1 to 2 centimeters long). The surgeon will 
remove a lymph node, which is about the size of a peanut, through the incision. The surgeon will 
then close the incision with stitches and bandage the wound. The whole process will take about 
30 to 40 minutes. You will remain under observation for 2-3 hours after the procedure. You will 
also be asked not to do any strenuous activities for the next 24 hours. You will need to return in 
about 1 week to have the stitches removed, depending on which type is used, and to assess the 
surgical site.  
4. 
How often is the lymph node biopsy done? 
You will be asked to undergo lymph node biopsy two times during this study at week 14 and 
week 58. 
5. 
What are the risks of lymph node biopsy? 
You may experience pain in the biopsy area once the local anesthetic has worn off. If you have 
pain, the study team will provide additional medications to control the pain. There is the 
possibility of some bleeding or bruising after the procedure. Doctors will perform blood tests 
before the biopsy and ask about any medications you are taking or conditions that could make 
you more likely to bleed. Surgery can cause a seroma to form which is a pocket of clear fluid that 
sometimes develops in the body after surgery.  There is a small risk of infection (less than 2%). 
If you have any concerns that your wound might be infected, you should contact the study team 
immediately. Signs of infection include redness, swelling, drainage, and heat at the incision. 
There is the possibility of developing a scar as the wound heals. There is a possibility of nerve 
injury during the procedure, which could result in either temporary or permanent reduction in 
feeling around the biopsy site. Finally, it is possible, although unlikely, that the surgeon will be 
unable to find a lymph node or for some reason unable to remove it during the procedure. If you 


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are willing, you may return at another visit for an attempt at lymph node biopsy on the other side 
of your body. 
 
 
Participants who develop complications after lymph node biopsy will receive immediate care at 
the CRC clinic, and where necessary, admitted for specialized at the Unilever Tea Kenya 
hospital. 
6. 
Will I have to pay anything to participate in this study? 
You will not have to pay for the procedures according to protocol.  
7. 
Will I receive any payment for my participation in this study? 
You will receive reimbursement for your transportation costs, time, and lost wages that may 
result from sick days taken after the procedure.You will receive reimbursement for the main 
study even if you don’t take part in any of the optional procedures.   
Reimbursement is as follows: 
 
• Mucosal collection:   1000 Ksh per each collection 
• Lymph node biopsy:  5000 Ksh 
 
8. 
Am I eligible to participate in the lymph node biopsy? 
You will not be able to participate in a lymph node biopsy if you have a bleeding disorder or if 
your platelet count is less than 150,000 count/ml or if, because of a medical condition, you are 
taking a blood thinner and you cannot stop it for 7 days before the procedure. You must have a 
negative pregnancy test if you are female.  Your body mass index must be less than 35. There 
may be other reasons why you would not be able to participate in the optional procedures. Your 
eligibility for lymph node biopsy will be decided by the study doctor after reviewing your 
medical history and physical exam.  
9. 
How do I prepare for the lymph node biopsy? 
You should not take certain medications that may affect coagulation (clotting), for instance, 
aspirins or non-steroidal anti-inflammatory drugs (e.g. ibuprofen and diclofenac) for 7 days 
before the procedure. Those medications could increase the risk of excessive bleeding.  
You should not eat for at least 8 hours (overnight) before the procedure.  
10. 
What will happen if I am injured? 
If you get sick or injured due to participation in this part of the study, you will receive 
appropriate medical treatment and care as provided with costs for such care covered by a limited 
fund and a clinical trials medical insurance policy. There is a limit to the amount of coverage 
available and, if the limit is exceeded, you may have to pay non-covered costs. 
KEMRI/USAMRD-A will pay costs up to the limit from set aside funds or through the 
insurance. However, you will not get any other compensation.  The U.S. National Institutes of 


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Health (NIH) does not have a mechanism to provide compensation for research-related injury.  
You are not waiving your rights by signing this consent form.  You should discuss this with the 
study doctor before deciding to participate in this part of the study.  If you have any questions 
about study-related sickness or injury contact the study doctor. 
11. 
What will happen to my samples?  
The samples from these optional procedures will be stored at KEMRI/USAMRD-A.  They will 
not have your name but rather will be assigned a number and no one in the laboratory will know 
any personal information about you.  Parts of your stored samples will be sent to study 
collaborators in the US and Thailand.  
 
You can decide whether to let us use your samples for future tests that are not covered under this 
research study. Your decision does not affect your participation in the study or any care you 
receive at this clinic.  Your decisions on what to do with your samples are on the “main” study 
consent form.  
12. 
Can I change my mind about participating in this part of the study? 
Yes. You can decide not to participate in this optional part of the study at any time, for any 
reason.  If you decide to not participate in this part of the study, it will not affect your 
participation in the main study or the care you receive from this or any other health care facility.  
 
13. 
How do I confirm my decision to be in this part of the study? 
Consent for Lymph Node Biopsy 
Please check the box of your choice and initial to the right on the blank provided. 
 
The procedure has been explained to me and I have had a chance to have all of my questions 
answered. The risks of the procedure have also been explained to me and I understand that 
there are risks with any medical procedure. 
 
________Yes, I agree to the lymph node biopsy procedure.  
          (initials) 
 
________No, I do not agree to the lymph node biopsy procedure.  
          (initials) 
Consent for Mucosal Secretion Collection 
 
Please check the box(s) of your choice and initial to the right on the blank provided.  You may 
choose one, both or none of the procedures. 
 
The procedures have been explained to me and I have had a chance to have all of my questions 
answered. The risks of the procedure have also been explained to me and I understand that 


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there are risks with any medical procedure. 
 
I agree to the mucosal collection procedure(s) specified below.          
 
________vaginal secretion collection (women only) 
            (initials) 
 
________semen collection (men only)    
           (initials) 
 
________rectal secretion collection 
           (initials) 
 
________No, I do not agree to any secretion collection.  
           (initials) 
 
Additional information about the trial is available at http://www.ClinicalTrials.gov website. 
SIGNATURE OF PARTICIPANT  
 
 
________________________________________ 
Printed Name of Participant 
 
 
________________________________________  
______________ 
Signature of Participant 
 
 
 
 
 
Date 
 
 
SIGNATURE OF INDIVIDUAL ADMINISTERING CONSENT 
(Can only be signed by an investigator or staff approved to administer consent) 
 
 
________________________________________ 
Printed Name of Administering Individual 
 
 
________________________________________  
______________ 
Signature of Administering Individual 
 
 
 
Date 
 
 


RV460 / WRAIR #2672 
 
Version 4.0 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
17 May 2021 
________________________________________________________________________________________________________ 
Page 153 of  204 
 
PHOTOGRAPHY CONSENT FORM  


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
04 August 2020 
  Consent for Photography and Use of Photos 
Page 1 of 2 
Kenya Medical Research Institute (KEMRI)  
United States Army Medical Research Directorate-Africa (USAMRD-A) 
In Collaboration with 
US Military HIV Research Program and the 
US Department of Defense (DoD) 
 
RV460/WRAIR #2672 Informed Consent Form for Photography and Use of 
Photos 
 
Protocol Title: 
A Randomized, Double-Blind Phase 1 Trial to Evaluate the Safety and 
Immunogenicity of Priming with Env-C Plasmid DNA Vaccine Alone, 
with Different Adjuvants, or with an Adjuvanted HIV Env gp145 C.6980 
Protein Vaccine and Boosting with the Adjuvanted HIV Env gp145 
C.6980 Protein Vaccine with or without the Env -C Plasmid DNA Vaccine 
in Healthy HIV Uninfected Adults in Kenya 
Sponsor: 
National Institute of Allergy and Infectious Diseases (NIAID), Division 
of AIDS (DAIDS) Bethesda, Maryland US  
 
Funding: 
United States Army Medical Research Acquisition Activity  
U.S. Military HIV Research Program   
Henry M. Jackson Foundation for the Advancement of Military Medicine  
Principal 
Investigator: 
Dr. Josphat Kosgei, MBCHB, MSc 
A photograph may be helpful to document an unusual or unexpected finding after the 
experimental vaccination is given. Also, if you undergo lymph node biopsy, the study doctor 
may take pictures of the biopsy site immediately after the procedure and again about 6 months 
later to document how well your biopsy site healed and for possible use as educational material 
for other participants who undergo the same procedure.  
 
No one will be able to determine your identity from these pictures. 
 
By signing below, you give study doctors permission to take and use photos taken of you during 
the study 
 
Refusing to give consent for use of your photos will not affect your participation in this study. If 
you give consent today, you can withdraw your consent at any time without consequences. 
 
Additional information about the trial is available at http://www.ClinicalTrials.gov website. 
 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
04 August 2020 
  Consent for Photography and Use of Photos 
Page 2 of 2 
Please check the box of your choice and initial to the right on the blank provided. 
 
________ Yes, I agree to allow my photos to be used. 
          (initials) 
 
________ No, I do not agree to allow my photos to be used.  
          (initials) 
 
SIGNATURE OF PARTICIPANT  
 
 
________________________________________ 
Printed Name of Participant 
 
 
________________________________________  
______________ 
Signature of Participant 
 
 
 
 
 
Date 
 
 
SIGNATURE OF INDIVIDUAL ADMINISTERING CONSENT 
(Can only be signed by an investigator or staff approved to administer consent) 
 
 
________________________________________ 
Printed Name of Administering Individual 
 
 
________________________________________  
______________ 
Signature of Administering Individual 
 
 
 
Date 
 


RV460 / WRAIR #2672 
 
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Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
17 May 2021 
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WITHDRAWAL OF CONSENT FORM 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for HIV-1 Env DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
04 August 2020 
 
 
Page 1 of 2 
Kenya Medical Research Institute (KEMRI)  
United States Army Medical Research Directorate-Africa (USAMRD-A) 
In Collaboration with 
U.S. Military HIV Research Program and the 
U.S. Department of Defense (DoD) 
 
RV460/WRAIR #2672 Withdrawal of Consent of  
Sample Storage for Future Use 
 
Protocol Title: 
A Randomized, Double-Blind Phase 1 Trial to Evaluate the Safety and 
Immunogenicity of Priming with Env-C Plasmid DNA Vaccine Alone, 
with Different Adjuvants, or with an Adjuvanted HIV Env gp145 C.6980 
Protein Vaccine and Boosting with the Adjuvanted HIV Env gp145 
C.6980 Protein Vaccine with or without the Env -C Plasmid DNA Vaccine 
in Healthy HIV Uninfected Adults in Kenya 
Sponsor: 
National Institute of Allergy and Infectious Diseases (NIAID), Division 
of AIDS (DAIDS) Bethesda, Maryland USA  
 
Site: 
Kenya Medical Research Institute (KEMRI) United States Army  
 
Principal 
Investigator:  
Dr. Josphat Kosgei, MBCHB, MSc 
 
Participant statement of withdraw of consent to have samples stored for future testing: 
 
I wish to withdraw my consent to have my biological samples stored for future use, including 
genetic testing.  
 
Please check the box next to your choice and write your initials on the line. 
____ 
   initials 
I wish to withdraw my consent for genetic testing only and continue to allow my 
samples to be stored and used for research in the future. 
____ 
   initials 
I wish to withdraw my consent for researchers to store and use my biological samples 
including genetic testing for research in the future.  
 
We will ask the storage facility to destroy any remaining samples that still have your study ID on 
them so that they cannot be used for future research.  Samples that are “deidentified”, meaning 
they do not have your study ID on them, will not be withdrawn from storage because, without 
your ID, there is no way for the researchers to find your samples. 
 
It has been explained to me that by signing this form, my samples will be used for all the tests 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for HIV-1 Env DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
04 August 2020 
 
 
Page 2 of 2 
specified for this present study, but no specimens will be stored for future use. 
 
I understand that withdrawing my consent to have my samples stored for future use will not 
make any difference to the care I am receiving now or in the future, or to any benefits that I am 
entitled to. 
 
I have been given a chance to ask all the questions that I have about withdrawing my consent to 
have my samples stored. All of my questions were answered to my satisfaction.  
 
Additional information about the trial is available at http://www.ClinicalTrials.gov website. 
 
SIGNATURE OF PARTICIPANT  
 
 
________________________________________ 
Printed Name of Participant 
 
 
________________________________________  
______________ 
Signature of Participant 
 
 
 
 
 
Date 
 
 
SIGNATURE OF INDIVIDUAL ADMINISTERING CONSENT 
(Can only be signed by an investigator or staff approved to administer consent) 
 
 
________________________________________ 
Printed Name of Administering Individual 
 
 
________________________________________  
______________ 
Signature of Administering Individual 
 
 
 
Date 
 


RV460 / WRAIR #2672 
 
Version 4.0 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
17 May 2021 
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TEST OF UNDERSTANDING 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
04 August 2020 
 
Page 1 of 2 
RV460/WRAIR #2672 
 
Test of Understanding 
 
True  False  1. 
Volunteers in this vaccine study will be protected against HIV.  
True  False  2. 
You will need to come to the clinic for 26 scheduled visits (including this one) 
over the next 2 years.  
True  False  3. 
The vaccines in this study will give you HIV.  
True  False  4. 
One purpose of this study is to determine if these vaccines are safe to administer 
to humans.  
True  False  5. 
Participants in this study will need to avoid engaging in activities that may expose 
them to HIV infection.    
True  False  6. 
You may take other experimental (test) products while you are taking part in this 
study.  
True  False  7. 
You may withdraw from the study at any time if you choose or your participation 
may be stopped if the study team decides it is in your best interest.  
True  False  8. 
Women are asked to not become pregnant while in the study.  
True  False  9. 
A participant in this study may experience side effects after vaccination.  
True  False  10. 
Because the vaccines may turn some of the standard tests for HIV infection 
positive, some people may incorrectly think that the study participants are 
infected with HIV (false-positive).    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
04 August 2020 
 
Page 2 of 2 
 
 
RV460/WRAIR #2672 
 
Answer Key 
 
False  
1. 
True 
2. 
False  
3. 
True 
4. 
True 
5. 
False  
6. 
True  
7. 
True  
8. 
True  
9. 
True  
10. 
 
 
 


RV460 / WRAIR #2672 
 
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Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
17 May 2021 
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Page 162 of  204 
 
PARTICIPANT VISIT SCHEDULE 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
                 Version 4.0 
               17 May 2021 
  Participant Visit Schedule 
Page 1 of 4 
RV460/WRAIR #2672 
Appendix G 
Participant Visit Schedule 
 
Visit 
No. 
Visit  
Day 
Clinic visit activities 
Optional 
Procedures 
Approx.  
Time 
Reimbursement 
Screening 
-45 to -3 days 
Screening: 
Briefing & contact information, 
informed consents, test of 
understanding, medical history, 
vital signs, complete physical 
exam, 1 TBSP blood draw for: 
HIV test, hepatitis B and C 
syphilis, general health, urine 
pregnancy test for women, urine 
test (dipstick) for blood and 
protein 
-Pap smear for 
women who agree 
to vaginal 
secretion 
collection 
4-5 
Hours 
1000 Ksh 
1 
0 
Vaccination 1*: 
Enrollment & randomize, exam & 
eligibility review, vaccination or 
placebo, examine injection site 
30-60 minutes post-injection, 
receive diary card, urine 
pregnancy test for women, 12 
TBSP blood draw for: research 
tests & HIV  
-Mucosal secretion 
collection  
5 - 6 
Hours 
1000 Ksh  
(+1000 Ksh for 
each mucosal 
secretion 
collection) 
Phone call or Clinic Visit 24-48 hours After Vaccination 
1000 Ksh 
2 
3 
Follow Up:  exam & symptom 
review, review diary card, 2 
TBSP blood draw for: research 
tests. Bring diary card. 
 
2 Hours 
1000 Ksh 
3 
7 
Follow Up:  exam & symptom 
review, review & collect diary 
card, 2 TBSP blood draw for: 
research tests. Bring diary card. 
 
3 Hours 
1000 Ksh 
4 
14 
Follow Up:  exam & symptom 
review, 5 TBSP blood draw for: 
general health & research tests 
 
2 Hours 
1000 Ksh 
5 
28 
Vaccination 2*: 
Exam & eligibility review, 
vaccination or placebo, examine 
injection site 30-60 minutes post-
injection, receive diary card, urine 
pregnancy test for women, 2 
TBSP blood draw for: research 
tests 
 
4 Hours 
1000 Ksh 
Phone call or Clinic Visit 24-48 hours After Vaccination 
1000 Ksh 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
                 Version 4.0 
               17 May 2021 
  Participant Visit Schedule 
Page 2 of 4 
Visit 
No. 
Visit  
Day 
Clinic visit activities 
Optional 
Procedures 
Approx.  
Time 
Reimbursement 
6 
35 
Follow Up:  exam & symptom 
review, Review diary card, 2 
TBSP blood draw for: research 
tests. Bring diary card. 
 
2 Hours 
1000 Ksh 
7 
42 
Follow Up:  exam & symptom 
review, 4 TBSP blood draw for: 
research tests and general health. 
Urine pregnancy test for women 
that elect for optional 
procedure(s). Bring diary card. 
-Mucosal  
Secretion 
collection  
4 - 5 
hours 
1000 Ksh  
(+1000 Ksh for 
each mucosal 
secretion 
collection) 
8 
84 
Vaccination 3*: 
Exam & eligibility review, 
vaccination or placebo, examine 
injection site 30-60 minutes post-
injection, receive diary card, urine 
pregnancy test for women, 3 
TBSP blood draw for: research 
tests 
 
4 Hours 
1000 Ksh 
Phone call or Clinic Visit 24-48 hours After Vaccination 
1000 Ksh 
9 
87 
Follow Up:  exam & symptom 
review, review diary card, 2 
TBSP blood draw for: research 
tests. Bring diary card. 
 
2 Hours 
1000 Ksh 
10 
91 
Follow Up:  exam & symptom 
review, review & collect diary 
card, 4 TBSP blood draw for: 
research tests. Bring diary card. 
 
3 Hours 
1000 Ksh 
11 
98 
Follow Up:  exam & symptom 
review, 9 TBSP blood draw for: 
general health, HIV & research 
tests. Urine pregnancy test for 
women that elect for optional 
procedure(s). 
-Mucosal secretion 
collection 
 
-Lymph node 
biopsy 
5 - 6 
Hours 
1000 Ksh  
(+1000 Ksh for 
each mucosal 
secretion 
collection & 5000 
Ksh for lymph 
node biopsy) 
Return in 1 week if lymph node biopsy was performed 
12 
140 
Vaccination 4*: 
Exam & eligibility review, 
vaccination or placebo, examine 
injection site 30-60 minutes post-
injection, receive diary card, urine 
pregnancy test for women, 3 
TBSP blood draw for: research 
tests 
 
4 Hours 
1000 Ksh 
Phone call or Clinic Visit 24-48 hours After Vaccination 
1000 Ksh 
13 
143 
Follow Up:  exam & symptom 
review, review diary card, 2 
 
2 Hours 
1000 Ksh 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
                 Version 4.0 
               17 May 2021 
  Participant Visit Schedule 
Page 3 of 4 
Visit 
No. 
Visit  
Day 
Clinic visit activities 
Optional 
Procedures 
Approx.  
Time 
Reimbursement 
TBSP blood draw for: research 
tests. Bring diary card. 
14 
147 
Follow Up:  exam & symptom 
review, review & collect diary 
card, 3 TBSP blood draw for: 
research tests. Bring diary card. 
 
3 Hours 
1000 Ksh 
15 
154 
Follow Up:  exam & symptom 
review, 9 TBSP blood draw for: 
general health, HIV & research 
tests. Urine pregnancy test for 
women that elect for optional 
procedure(s). 
-Mucosal secretion 
collection  
4 - 5 
hours 
1000 Ksh  
(+1000 Ksh for 
each mucosal 
secretion 
collection) 
16 
224 
Vaccination 5*: 
Exam & eligibility review, 
vaccination or placebo, examine 
injection site 30-60 minutes post-
injection, receive diary card, urine 
pregnancy test for women, blood 
draw for: 2 TBSP research tests 
 
4 hours 
1000 Ksh 
Phone call or Clinic Visit 24-48 hours After Vaccination 
1000 Ksh 
17 
231 
Follow Up:  exam & symptom 
review, review diary card, 3 
TBSP blood draw for: research 
tests. Bring diary card. 
 
2 Hours 
1000 Ksh 
18 
238   
Follow Up:  exam & symptom 
review, 9 TBSP blood draw for: 
research tests, general health & 
HIV. Bring diary card. Urine 
pregnancy test for women that 
elect for optional procedure(s). 
-Mucosal secretion 
collection  
4 - 5 
Hours 
1000 Ksh  
(+1000 Ksh for 
each mucosal 
secretion 
collection) 
19 
392 
Vaccination 6*: 
Exam & eligibility review, 
vaccination or placebo, examine 
injection site 30-60 minutes post-
injection, receive diary card, urine 
pregnancy test for women, 3 
TBSP blood draw for: research 
tests 
 
4 Hours 
1000 Ksh 
Phone call or Clinic Visit 24-48 hours After Vaccination 
1000 Ksh 
20 
395 
Follow Up:  exam & symptom 
review, review diary card, 2 
TBSP blood draw for: research 
tests. Bring diary card. 
 
2 Hours 
1000 Ksh 
21 
399  
Follow Up:  exam & symptom 
review, review & collect diary 
card, 5 TBSP blood draw for: 
research tests & HIV. Bring diary 
card. 
3 Hours 
1000 Ksh 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
                 Version 4.0 
               17 May 2021 
  Participant Visit Schedule 
Page 4 of 4 
Visit 
No. 
Visit  
Day 
Clinic visit activities 
Optional 
Procedures 
Approx.  
Time 
Reimbursement 
22 
406 
Follow Up:  exam & symptom 
review, 11 TBSP blood draw for: 
general health & HIV & research 
tests. Urine pregnancy test for 
women that elect for optional 
procedure(s).  
-Mucosal secretion 
collection 
 
-Lymph node 
biopsy 
5 - 6 
Hours 
1000 Ksh  
(+1000 Ksh for 
each mucosal 
secretion 
collection & 5000 
Ksh for lymph 
node biopsy) 
Return in 1 week if lymph node biopsy was performed 
23 
476 
Follow Up:  exam & symptom 
review, 9 TBSP blood draw for: 
research tests. Urine pregnancy 
test for women that elect for 
optional procedure(s). 
-Mucosal secretion 
collection  
4 - 5 
Hours 
1000 Ksh  
(+1000 Ksh for 
each mucosal 
secretion 
collection) 
24 
560 
Follow Up:  exam & symptom 
review, 9 TBSP blood draw for: 
research tests & HIV. Urine 
pregnancy test for women that 
elect for optional procedure(s). 
-Mucosal secretion 
collection  
 
4 - 5 
Hours 
1000 Ksh  
(+1000 Ksh for 
each mucosal 
secretion 
collection) 
25 
728 
Follow Up:  exam & symptom 
review, 9 TBSP blood draw for: 
research tests & HIV. Urine 
pregnancy test for women that 
elect for optional procedure(s). 
-Mucosal secretion 
collection  
 
4 - 5 
Hours 
1000 Ksh  
(+1000 Ksh for 
each mucosal 
secretion 
collection) 
26 
Exit 
735 
Final visit: exam & symptom 
review, 4 TBSP blood draw for: 
research tests 
2 Hours 
1000Ksh 
 
 
Reimbursement 
Study visits:  1000 Ksh 
Unscheduled visits:  Up to 500 Ksh, at the discretion of the study doctor 
Mucosal collection:  1000 Ksh per each collection 
Lymph node biopsy: 5000 Ksh 
Transportation: Up to 3000 Ksh, at the discretion of the study doctor 
* A study vaccination may be given outside your vaccination window if the protocol safety 
review team (PSRT) permits.   


RV460 / WRAIR #2672 
 
Version 4.0 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
17 May 2021 
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RISK ASSESSMENT TOOL 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
04 August 2020 
 
Page 1 of 1 
WRAIR #2672/RV460 HIV Risk Assessment Tool 
 
PID: __ __ __ __ __               Date: __ __/__ __ __/__ __ __ __ 
Visit: _____                    
 
SEXUAL BEHAVIOURS 
 
A participant may be appropriate for inclusion if he or she meets these guidelines: 
 
Criteria 
A participant in the last 12 months:  
Yes 
No 
1.  
Did not have oral, vaginal, or anal intercourse with an HIV-
infected partner, or a partner who uses injection drugs. 
 
 
2.  
Did not give or receive money, drugs, gifts, or services in 
exchange for oral, vaginal, or anal sex 
 
 
3.  
Has not been diagnosed and/or been treated for a sexually 
transmitted infection: OR have not had any of the sexually 
transmitted infection symptoms as assessed by the study 
doctor/clinician. 
 
 
Criteria In the last 6 months:  
1.  
Has abstained from penile/anal or penile/vaginal intercourse.OR 
had 2 or fewer partners of the opposite birth sex for vaginal and/or 
anal intercourse. 
 
 
2.  
Is not an MSM or a transgender person. 
 
 
3.  
Uses or intends to use condoms in situations which may include 
penile/anal or penile/vaginal intercourse with new partners, 
partners of unknown HIV status, occasional partners, partners 
outside a primary relationship, and/or partners known to have 
other partners. 
 
 
NON-SEXUAL BEHAVIOURS 
Criteria 
A participant who in the last 12 months: 
 
 
1.  
Did not inject drugs or other substances without a prescription. 
 
 
2.  
Did not use cocaine, methamphetamine, or excessive alcohol, 
which in the investigator’s judgment, rendered the participant at 
greater than low risk for acquiring HIV infection 
 
 
Comments: 
 
 
 
Signature of Investigator or Designee 
Date 
 
 


RV460 / WRAIR #2672 
 
Version 4.0 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
17 May 2021 
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Page 169 of  204 
 
DIARY CARD 


LABEL 
      Diary Card   
               Participant ID:  |_4_|_6_|_0_|-|__|__|__|__|   
Vacc. #: ____   
Vaccination Date:    
____ 
____ 
____ 
DD 
MM 
YYYY 
 
Short title: Comparative Adjuvant Study for HIV-1 Env DNA and Protein Vaccines in Kenya  
RV460 / WRAIR #2672 
 
 
 
13-07-2020   
Version 1.7 
 
Page 1 of 2 
 
Instruction for recording No. 2-7 and 8-15 
Please use the grading scale below to record the severity of your reaction to the injections in the next sections: 
0 = None 
1 = Mild: minimal interference with usual social and functional activities.  
2 = Moderate: symptoms causing greater than minimal interference with usual social and functional activities.  
3 = Severe:  symptoms causing inability to perform usual social and functional activities 
Time After vaccination 
30-60 
min 
6 hr 
Day 1 
Day 2 
Day 3 
Day 4 
Day 5 
Day 6 
Day 7 
Day/Month 
__ /__ 
__ /__ 
__ /__ 
__ /__ 
__ /__ 
__ /__ 
__ /__ 
__ /__ 
__ /__ 
Time taken (hrs/min) 
 
 
 
 
 
 
 
 
 
1. Oral temperature (Celsius) 
 
 
 
 
 
 
 
 
 
Vaccination injection site reactions 
 
 
Right arm 
 
 
Left arm 
2. Injection site pain or tenderness 
 
 
 
 
 
 
 
 
 
3. Swelling (at injection site) 
 
 
 
 
 
 
 
 
 
4. Itching (at injection site) 
 
 
 
 
 
 
 
 
 
5. Redness (measure the largest 
dimension in cm.) 
 
 
 
 
 
 
 
 
 
6. Hardness (measure the largest 
dimension in cm.) 
 
 
 
 
 
 
 
 
 
7. Warmth (at injection site) 
 
 
 
 
 
 
 
 
 
General Reactions (not injection site) 
 
8. Headache 
 
 
 
 
 
 
 
 
 
9. Chills 
 
 
 
 
 
 
 
 
 
10. Dizziness 
 
 
 
 
 
 
 
 
 
11. Tiredness / Fatigue 
 
 
 
 
 
 
 
 
 
12. Nausea 
 
 
 
 
 
 
 
 
 
13. Muscle pain 
 
 
 
 
 
 
 
 
 
14. Joint pain 
 
 
 
 
 
 
 
 
 
15. Rash (if present, describe in “other 
symptoms”  
 
 
 
 
 
 
 
 
 
16. Took medication for 
fever or for above 
symptoms? 
0=No 
1=Yes 
 
 
 
 
 
 
 
 
 
Other symptoms (please describe): 
 
 
 
 
 
 
 
 
 


LABEL 
      Diary Card   
               Participant ID:  |_4_|_6_|_0_|-|__|__|__|__|   
Vacc. #: ____   
Vaccination Date:    
____ 
____ 
____ 
DD 
MM 
YYYY 
 
Short title: Comparative Adjuvant Study for HIV-1 Env DNA and Protein Vaccines in Kenya  
RV460 / WRAIR #2672 
 
 
 
13-07-2020   
Version 1.7 
 
Page 2 of 2 
 
 
If you take any medication, please record in the table below 
If you take medications for fevers, please check your temperature again after 4 hours and record above in “Other 
symptoms” 
Medication 
Dose/route 
Reason 
Start date 
Stop date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Suggestion 
 
• 
Complete the diary card in as much detail as you can every day, at the same time each day 
• 
Record any problems that occur during this period 
• 
Bring back this diary card with you at the next appointment 
• 
If you forget to record any data, leave it blank 
 
If you have any problems or questions, please contact: 
 
Staff name _________________________________ 
Telephone Number ______________ 
 
 
If you received a “patch” over the vaccination site 
on your upper arm, please write the time you 
removed the “patch” in the space below. You will 
need to wear the patch for 6 hours ± 2 hours (range 
4-8 hours) after application.  
 
Time patch was removed: ______________ (hrs/min)   
 
 
Official use only 
 
Card completed by participant and not edited by staff 
 
 
Card completed by participant and edited by: 
__________________________ 
____ 
____ 
____ 
 
Staff name 
DD 
MM 
YYYY 
 
 


RV460 / WRAIR #2672 
 
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Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
17 May 2021 
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Page 172 of  204 
 
EMERGENCY CONTACT CARD 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
04 August 2020 
   Emergency Contact Card 
Page 1 of 1 
Emergency Contact Card 
 
RV460 / WRAIR #2672                       HIV Vaccine Study 
 
Participant ID# __________________________ 
Cardholder is a participant in an HIV VACCINE study 
conducted at KEMRI 
 
While in this study, false-positive HIV serology can occur, but 
no infection will be present.  
If this volunteer develops any unexplained illness or symptoms 
that could possibly be related to vaccination or other study 
procedure, please contact: 
Rael Bor (0)5220 36329 or (0)0729110121 
 
 
RV460 / WRAIR #2672                       HIV Vaccine Study 
 
Participant:  Please keep this card with you so that 
you can contact the study team if you have any 
problems, questions, or are concerned about a 
symptom.  
 
Dr. Josphat Kosgei 
 
(0)5220 36302   or   (0)729 110 122 
 
or his research staff    (0) 5220) 36000/100 
 
 


RV460 / WRAIR #2672 
 
Version 4.0 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
17 May 2021 
________________________________________________________________________________________________________ 
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VISP LETTER 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
04 August 2020 
 
Page 1 of 1 
 
KENYA MEDICAL RESEARCH 
INSTITUTE 
US ARMY MEDICAL RESEARCH 
DIRECTORATE - AFRICA 
Kenya Medical Research Institute (KEMRI) 
P.O. Box 606, 00621 Villages Mkt. 
Tel: 2729303, 2719694 Fax: 2714592 
E-mail: info@usamru-k.org 
 
 
WRAIR #2672/RV460 VISP Letter  
Certificate of Participation 
 
Date: __________________ 
 
To Whom it May Concern, 
 
The undersigned, Dr. Josphat Kosgei, hereby confirms that: 
Mr./Mrs./Ms.  
                                  , date of birth      /      /     , has been participating as a 
healthy, HIV-uninfected volunteer in  clinical research study called: “A Randomized, Double-Blind Phase 
1 Trial to Evaluate the Safety and Immunogenicity of Priming with Env-C Plasmid DNA Vaccine Alone, 
with Different Adjuvants, or with an Adjuvanted HIV Env gp145 C.6980 Protein Vaccine and Boosting 
with the Adjuvanted HIV Env gp145 C.6980 Protein Vaccine with or without the Env -C Plasmid DNA 
Vaccine in Healthy HIV Uninfected Adults in Kenya” at the Kenya Medical Research Institute (KEMRI) 
United States Army Medical Research Directorate-Africa (USAMRD-A) from_________ to 
___________ (date). This participant was vaccinated in a double-blinded manner with either Env-C 
Plasmid DNA, or HIV Env gp145 C.6980 protein, or placebo, depending on the study arm to which the 
volunteer was randomized. 
As a consequence, if the participant received active study vaccine, HIV-specific antibodies might have 
developed as a result of an immune response to the candidate HIV vaccine regimen. Therefore, the results 
obtained in this person with commonly used HIV screening tests should be interpreted with caution as the 
outcome of the test could be positive without the participant truly being infected with HIV. 
The research center uses special HIV testing algorithm to differentiate a positive test with no natural HIV 
infection from a natural HIV infection. If the HIV testing is required, the research center should be 
contacted for guidance or assistance in testing. 
 
If you require any further clarification, please contact:  
Dr. Josphat K. Kosgei, MBChB, MSc, DLSHTM 
Kenya Medical Research Institute/Walter Reed Project HIV Program 
P.O. Box 1357-20200, Hospital Road, Kericho, Kenya Tel: +254 5220 30686/ +254 5220 30388 
 
Additional information about the trial is available at http://www.ClinicalTrials.gov website. 
 
Yours sincerely, 
 
_______________________________________________________________ 
Dr. Josphat K. Kosgei, MBChB, MSc, DLSHTM, Principal Investigator 


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UNBLINDING LETTER 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
04 August 2020 
  Unblinding Letter 
Page 1 of 3 
 
KENYA MEDICAL RESEARCH 
INSTITUTE 
US ARMY MEDICAL RESEARCH 
DIRECTORATE - AFRICA 
Kenya Medical Research Institute (KEMRI) 
P.O. Box 606, 00621 Villages Mkt. 
Tel: 2729303, 2719694 Fax: 2714592 
Email: info@usamru-k.org 
 
 
WRAIR #2672/RV460 Unblinding Letter 
Date: __________________ 
 
Dear Participant, 
 
Thank you, once again, for participating in this clinical trial. You may recall that the purpose of this study 
was to see if the experimental HIV vaccines are safe (if it causes any side effects and how well it is 
tolerated).  As we complete the data analysis, we can tell you whether you received the placebo or study 
vaccines in this trial.   
 
Note: The study physician will edit this letter and only include the treatment that the individual 
received.  
 
Number of doses received: _________ 
 
For Placebo Recipients: 
During the course of the trial, you received what is called the “Placebo.  This consisted of an inactive 
substance—like salt water injections.  The liquid used as the placebo was saline (salt water).  You did not 
receive any experimental vaccine product during your participation in the trial." 
 
 
Or 
 
 
For Group 1 Recipients:  
During the course of the trial, you received the study experimental products called Env-C Plasmid DNA 
(HIV-1 gp120 (93MW965.26) DNA) and HIV Env gp145 C.6980 protein vaccines and the adjuvant, 
Rehydragel ®. In this group, Rehydragel was given at the last three time points of immunization. The fact 
that you received the experimental vaccines does not mean that you are protected from HIV infection, and 
you should continue to prevent HIV exposure.  
   
Or 
 
For Group 2 Recipients:  
 
During the course of the trial, you received the study experimental products called Env-C Plasmid DNA 
(HIV-1 gp120 (93MW965.26) DNA) and HIV Env gp145 C.6980 protein vaccines and two adjuvants 
called ALF43 and Rehydragel ®. Both adjuvants were given at the last three time points of immunization.  
The fact that you received the experimental vaccines does not mean that you are protected from HIV 
infection, and you should continue to prevent HIV exposure.  
 


RV460 / WRAIR #2672 
 
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            Or 
 
For Group 3 Recipients:  
During the course of the trial, you received the study experimental products called Env-C Plasmid DNA 
(HIV-1 gp120 (93MW965.26) DNA) and HIV Env gp145 C.6980 protein vaccines and two adjuvants 
called dmLT and Rehydragel ®. The dmLT was given at the first three time points of immunization and 
Rehydragel ®. was given at the last three time points of the immunization. The fact that you received the 
experimental vaccines does not mean that you are protected from HIV infection, and you should continue 
to prevent HIV exposure. 
 
            Or 
 
For Group 4 Recipients: 
During the course of the trial, you received the study experimental products called Env-C Plasmid DNA 
(HIV-1 gp120 (93MW965.26) DNA) and HIV Env gp145 C.6980 protein vaccines and three adjuvants 
called dmLT, ALF43 and Rehydragel ®. The dmLT was given at the first three time points of 
immunization and ALF43 and Rehydragel ® were given at the last three time points of immunization. The 
fact that you received the experimental vaccines does not mean that you are protected from HIV infection, 
and you should continue to prevent HIV exposure. 
           
             Or 
 
For Group 5 Recipients: 
During the course of the trial, you received the study experimental products called Env-C Plasmid DNA 
(HIV-1 gp120 (93MW965.26) DNA) and HIV Env gp145 C.6980 protein vaccines and two adjuvants 
called Rehydragel ® and ALF43. ALF43 was given at the first three time points of immunization and 
Rehydragel ® was given at the last three time points of immunization. The fact that you received the 
experimental vaccines does not mean that you are protected from HIV infection, and you should continue 
to prevent HIV exposure. 
 
             Or 
 
For Group 6 Recipients: 
During the course of the trial, you received the study experimental products called Env-C Plasmid DNA 
(HIV-1 gp120 (93MW965.26) DNA) and HIV Env gp145 C.6980 protein vaccines and two adjuvants 
called Rehydragel ®.and ALF43. ALF43 was given at all six time points of immunization and Rehydragel 
® was given at the last three time points.  The fact that you received the experimental vaccines does not 
mean that you are protected from HIV infection, and you should continue to prevent HIV exposure. 
              
Or  
 
For Group 7 Recipients: 
During the course of the trial, you received the study experimental products called Env-C Plasmid DNA 
(HIV-1 gp120 (93MW965.26) DNA) and HIV Env gp145 C.6980 protein vaccines, both vaccines were 
given at all six time points of immunization, and the two adjuvants called Rehydragel ®.and ALF43.  
ALF43 was given at all six time points of immunization and Rehydragel ® was given at the last three time 
points.  The fact that you received the experimental vaccines does not mean that you are protected from 
HIV infection, and you should continue to prevent HIV exposure. 
 
 
 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
04 August 2020 
  Unblinding Letter 
Page 3 of 3 
Please contact the clinic and/or Principal Investigator with any questions or concerns you may have. 
 
Yours sincerely, 
 
____________________________________________________________ 
Dr. Josphat K. Kosgei, MBChB, MSc, DLSHTM, Principal Investigator 
 
If you require any further clarification, please contact:  
Dr. Josphat K. Kosgei, MBChB, MSc, DLSHTM 
Kenya Medical Research Institute/Walter Reed Project HIV Program 
P.O. Box 1357-20200, Hospital Road, Kericho, Kenya Tel: +254 5220 30686/ +254 5220 30388 
 
Additional information about the trial is available at http://www.ClinicalTrials.gov website 


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ROLES AND RESPONSIBILITIES 


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Roles and Responsibilities 
Protocol Chair:  
Responsible for study design and serving as a liaison between the site, the vaccine developers 
including the Sponsor, and contributing support to overall project management and the analysis 
and reporting of study data.  The chair will support the site PI with clinical trial guidance, 
protocol preparation, protocol review and response to regulatory reviews. The Chairs do not have 
contact with study subjects.  
 
Protocol Co-Chair:  
Responsible for study design and serving as a liaison between the site and the vaccine developers 
including the Sponsor and contributing support to overall project management and the analysis 
and reporting of study data.  The Co-Chair will provide support with clinical trial guidance, 
protocol preparation, protocol review and response to regulatory reviews. The Chairs do not have 
contact with study subjects.  
 
Principal Investigator:  
Responsible for all aspects of the study at the site including performing briefing, consenting, and 
all other participant interactions, while maintaining the blind..  The principal investigator is the 
primary person responsible for individual participant safety. 
 
Associate Investigators at the Site:  
Assist the Protocol Chairs and Principal Investigators in performing briefing, consenting, and all 
other participant interactions under their supervision, while maintaining the blind.  Site associate 
investigators can act in place of the PI, if necessary.   
 
Associate Investigators at MHRP:  
Assist the Protocol Chairs and will not have contact with study subjects or identifiers. 
 
Laboratory Investigators:  
Responsible for laboratory analysis.  Lab investigators will not have contact with study subjects 
or identifiers.  
 
Protocol Statistician:  
Responsible for statistical analysis for this study. The protocol statistician will not have contact 
with study subjects.  
 
Overall Study Pharmacist:  
The qualified pharmacist with responsibility for overseeing the import, distribution, inventory, 
and accountability of vaccine, communication with sponsor/MHRP regarding pharmacy related 
issues, training and consultation with the study site pharmacy personnel. 
 
Protocol Data Management:  
Responsible for data management for this study.  The data management team will not have 
contact with study subjects.  
 


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DAIDS Medical Officer:  
Responsible for protocol development and liaison for the submission to the DAIDS Clinical 
Sciences Review Committee review The DAIDS medical officer will not have contact with study 
subjects or identifiers. 
 
DoD Research Monitor: 
The DoD Research Monitor may perform oversight functions (e.g. observe recruitment, 
enrollment procedures, and the consent process for participants; oversee study interventions and 
interactions; review monitoring plans and UPIRTSO reports; oversee data collection, and 
analysis) and report their observations and findings to the IRB. The DoD research monitor may 
discuss the research protocol with the investigators, interview participants, and consult with 
others outside of the study about the research. The research monitor shall have authority to stop a 
research protocol in progress, remove individual participants from a research protocol, and take 
whatever steps are necessary to protect the safety and well-being of participants until the IRBs 
can assess the monitor's report. Research Monitors shall have the responsibility to promptly 
report their observations and findings to the IRB. The DoD Research Monitor is required to 
review all unanticipated problems involving risks to subjects or others, serious adverse event 
(SAE) reports, and all participant deaths. The DoD Research Monitor at a minimum must 
comment on the outcomes of the event or problem and in case of a serious adverse event or 
death, comments on the relationship to participation in the study. They must also indicate 
whether he/she concurs with the details of the report provided by the PI. 
 


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PARTICIPATING LABORATORIES 


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Participating Labs 
 
MHRP Laboratories 
508 Robert Grant Ave.   
Silver Spring, MD  
20910 USA 
 
MHRP/SPL Repository 
13 Taft Court 
Rockville, MD.  
20850 USA 
 
AFRIMS Laboratory 
Department of Retrovirology 
315/6 Rajvithi Rd. 
Bangkok 10400, Thailand 
 
Local Laboratory (Kenya): 
Kenya Medical Research Institute 
U.S. Army Medical Research Directorate-Africa 
Clinical Research Centre  
PO Box 1357, Off Hospital Rd. 
Kericho, Kenya 20200 
 
Back-up/Fee for service laboratories (Kenya): 
The Kenya Medical Research Institute/Walter Reed Project   
Clinical Research Center Laboratory  
Kombewa, Kisumu, Kenya  
 
Walter Reed Project/Kenya Medical Research Institute  
Along Kakamega Road PO Box 54 – 40100  
Kisumu, Kenya  
 
Kenya Medical Research Institute/Center for Disease Control (KEMRI/CDC) 
New Nyanza Provincial General Hospital Grounds,  
Off Kisumu-Kakamega Road  
Kisumu, 40100 Kenya 
 
Kenya Medical Research Institute/Walter Reed Project  
Clinical Research Centre Laboratory 
P.O. Box 1357 KERICHO 
Kericho, Kenya 
 


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AMPATH Reference Laboratory 
1st floor, West Wing 
Nandi Road, Moi Teaching and Referral Hospital Grounds, 
P.O Box 4606-30100, Eldoret, Kenya 
 
Aga Khan Health Services, Kenya 
Kericho Medical Centre, Ushma Plaza 
On Hospital/Temple Road, 
P.O. Box 530, Kisumu 40100, 
Tel: 052-2020623 
Email: ksm.admin@akhskenya.org 
  
Lancet Kericho Lab 
Sinendet Towers, 3rd Floor, 
Tel: 0703061176/0724658439, 
Email: Kericho@lancet.co.ke 
Kisumu-Kericho Road 
  
PathCare Kenya Ltd 
Regal Plaza, Limuru Road, 
P.O. Box 1256-00606, 
Nairobi, Kenya. 
Tel: 254 20 3753416-9/020-2430854/2430753 
Fax: 254 20 3753420 
 
Moi Teaching and Referral Histopathology Laboratory 
Moi Teaching & Referral Hospital 
P.O. Box 3-30100, Eldoret, Kenya. 
Nandi Road,Uasin Gishu County 
 
Chulalongkorn University 
1873 Rama 4 Road, Pathumwan 
Bangkok, 10330, Thailand 
 


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LIST OF PIMMCS 


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List of Potentially Immune-Mediated Medical Conditions 
 
 
Gastrointestinal  
• Celiac disease   
• Crohn’s disease  
• Ulcerative colitis  
• Ulcerative proctitis  
 
Liver   
• Autoimmune cholangitis   
• Autoimmune hepatitis  
• Primary biliary cirrhosis  
• Primary sclerosing cholangitis  
• Metabolic diseases  
• Addison’s disease  
• Autoimmune thyroiditis (including Hashimoto 
thyroiditis)  
• Diabetes mellitus type I  
• Grave's or Basedow’s disease      
 
Musculoskeletal 
 
• Dermatomyositis, Polymyositis and Antisynthetase 
Syndrome  
• Juvenile chronic arthritis (including Still’s disease)  
• Mixed connective tissue disorder   
• Polymyalgia rheumatic  
• Psoriatic arthropathy  
• Relapsing polychondritis  
• Rheumatoid arthritis  
• Scleroderma, including diffuse systemic form and 
CREST syndrome  
• Spondyloarthritis, including ankylosing spondylitis, 
reactive arthritis (Reiter's Syndrome) and 
undifferentiated spondyloarthritis  
• Systemic lupus erythematosus  


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• Systemic sclerosis   
 
Neuroinflammatory:  
• Acute disseminated encephalomyelitis, including site 
specific variants (e.g., non-infectious encephalitis, 
encephalomyelitis, myelitis, radiculomyelitis)   
• Cranial nerve disorders, including paralyses/paresis 
(e.g., Bell’s palsy)  
• Guillain-Barré syndrome, including Miller Fisher 
syndrome and other variants  
• Immune-mediated peripheral neuropathies and 
plexopathies, including chronic inflammatory 
demyelinating polyneuropathy, multifocal motor 
neuropathy and polyneuropathies associated with 
monoclonal gammopathy  
• Multiple sclerosis  
• Narcolepsy  
• Optic neuritis  
• Transverse myelitis  
• Myasthenia gravis, including Eaton-Lambert syndrome 
 
Skin:   
 
• Alopecia areata   
• Autoimmune bullous skin diseases, including 
pemphigus, pemphigoid and dermatitis herpetiformis  
• Cutaneous lupus erythematosus  
• Erythema nodosum   
• Morphoea  
• Lichen planus  
• Psoriasis  
• Rosacea  
• Sweet’s syndrome   
• Vitiligo 
 


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Vasculitides: 
• Large vessels vasculitis including: giant cell arteritis 
such as Takayasu's arteritis and temporal arteritis  
• Medium sized and/or small vessels vasculitis including: 
polyarteritis nodosa, Kawasaki's disease, microscopic 
polyangiitis, Wegener's granulomatosis, Churg–Strauss 
syndrome (allergic granulomatous angiitis), Buerger’s 
disease thromboangiitis obliterans, necrotizing 
vasculitis and anti-neutrophil cytoplasmic antibody 
(ANCA) positive vasculitis (type unspecified), Henoch- 
Schonlein purpura, Behcet's syndrome, leukocytoclastic 
vasculitis  
 
Other: 
 
• Antiphospholipid syndrome 
• Asthma and other immune-based lung diseases such as 
idiopathic pulmonary fibrosis, BOOP   
• Autoimmune hemolytic anemia 
• Autoimmune glomerulonephritis (including IgA 
nephropathy, glomerulonephritis rapidly progressive, 
membranous glomerulonephritis, 
membranoproliferative glomerulonephritis, and 
mesangioproliferative glomerulonephritis)  
• Autoimmune myocarditis/cardiomyopathy   
• Autoimmune thrombocytopenia   
• Goodpasture syndrome   
• Pernicious anemia   
• Raynaud’s phenomenon* note: Up to 10% of healthy 
female population has this without ever developing an 
autoimmune disease 
• Sarcoidosis   
• Sjögren’s syndrome   
• Stevens-Johnson syndrome   
• Uveitis 
 


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EXTERNAL COLLABORATORS  


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External Collaborators 
 
Collaborator 
Role 
Access 
 
Shan Lu, MD, PhD 
University of Massachusetts 
Medical School  
Professor of Medicine 
55 Lake Ave. North,  
Worcester, MA 01655 
Phone: 508-856-6791 
Email: 
shan.lu@umassmed.edu 
 
• Performs potency assay 
for gp120 DNA.  
• Provides the gp120 DNA 
plasmid used in this trial 
• Subject matter expert on 
gp120 DNA 
• May assist with writing 
any publication 
 
No contact with study 
subjects, samples, or access 
to identifiable data.  
 


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TELEPHONE VISIT SCRIPT 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
 
Version 3.0 
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Page 1 of 1 
Telephone Visit Script 
Site staff may use the telephone script as guidance when carrying out a phone call visit. 
1) If you reach the participant: 
a) Introduce yourself. 
b) Ask if this is a good time for the participant to talk.  If so, proceed.  If not, try to ascertain 
a better time to call the participant back. 
c) State why you are calling with the following: “I am calling to see how you are doing 
since you received the vaccination”   
d) If the participant is silent or says something unrevealing such as “Everything is fine, ask 
the following: “Have you had any complaints?” OR “Are you able to carry out your daily 
activities without a problem?”   
e) If the participant identifies a symptom, try to take further history and, based on your 
judgement, provide remedy, or invite the participant to the clinic for further assessments. 
Participants with symptoms assessed to be grade 3 and above should be invited for 
further assessment at the clinic.  
f) If the participant identifies no symptoms; finish the call with a brief summary, such as 
“Thank you for your time and I would like to request that you continue filling the diary 
card and remember to come for your next appointment on the date that you were 
provided.”  
g) If the participant had a sign or symptom, and you want to evaluate the participant at the 
clinic, remind he/she to come to the clinic at the earliest opportunity. 
2) If you do not reach the participant and reach someone else or if connected to voice mail; 
a) Introduce yourself.  
b) If you reach someone else, ask if that person knows the participant and request that the 
participant calls back or ask the best time to call back to talk to the participant. 
c) In case of voicemail, leave a message for the participant to call back. 
d) Once the participant is reached, go through the procedure 1 and 2. 
3) Document the participant’s responses and your recommendations, if any, and attempts to 
contact the participant including time and date.  
 


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BRIEFING SLIDES 


1
RV460 
Protocol 
Briefing
Conducted by:
§ Kenya Medical Research 
Institute/Walter Reed Project
(KEMRI/WRP) 
§U.S. Military HIV Research 
Program (MHRP) 
Sponsored by:
§ National Institutes of Health:
National Institute of Allergy and Infectious 
Diseases (NIAID) Division of AIDS (DAIDS) 
1
1
Study Title: A Randomized, Double-Blind 
Phase 1 Trial to Evaluate the Safety and 
Immunogenicity of Priming with Env-C 
Plasmid DNA Vaccine Alone, with Different 
Adjuvants, or with an Adjuvanted HIV Env 
gp145 C.6980 Protein Vaccine and 
Boosting with the Adjuvanted HIV Env 
gp145 C.6980 Protein Vaccine with or 
without Env-C Plasmid DNA Vaccine in 
Healthy HIV Uninfected Adults in Kenya
Study Location: KEMRI Clinical Research 
Centre
Principal Investigator: Dr. Josphat Kosgei
2
2
Purpose of this Briefing
This Presentation will tell you details about the study so that you can 
decide if participation is right for you. 
The next slide lists key information and the slides following will give 
you more details.
We invite you to ask questions at any time.
Detailed information is included in Informed Consent Forms
3
3
Voluntary Consent. You are being asked to volunteer 
for a research study.  It is up to you whether you choose 
to participate or not.  There are no penalties and you will 
not lose anything if you decide not to join or, if after you 
join, you decide to quit.  
Purpose. We are doing this research to test a vaccine 
for HIV and vaccine additives called adjuvants that can 
help the vaccine be more effective.
Key Information
4
4
Duration. Your part of the study will last 105 weeks (26 
months).  You will be asked to complete at least 26 clinic 
visits. Additionally, you will be contacted by phone, once 
per week for three weeks to discuss any changes you 
may have experienced after the first 105 weeks of being 
in the study.
Procedures and Activities. We will ask you to receive 6 
doses of the experimental vaccines and monitor your 
blood and symptoms after each vaccine.  
More Key Information
5
5
Risks. Most studies have some possible harms that 
could happen to you if you join.  In this study, we expect 
you to have some mild or moderate symptoms like what 
happens after you receive some approved vaccines. 
Some examples of mild common and expected reactions 
are: fever, body aches, feeling tired and pain at the 
injection site.  It is very rare, but possible, to have a 
serious and life-threatening allergic reaction right after a 
vaccine is given.  Additionally, there is a chance that you 
could develop a serious illness such as an autoimmune 
disease, but this is also very rare. 
More Key Information
6
6


2
Benefits. You will not directly benefit from participating in 
this study.  The results of this study will be shared with 
researchers from around the world and could play a role 
in future HIV vaccine development which may be 
beneficial in the future for others.
Alternatives. Participation is voluntary, and the only 
alternative is to not participate.
More Key Information
7
7
Intro
We are doing this research to 
test a vaccine for HIV and 
vaccine additives, called 
adjuvants, that can help the 
vaccine be more effective.
Vaccines are a safe and 
effective way to prevent 
diseases, but we do not have a 
vaccine for every disease. HIV 
is one of the diseases that we 
still need a vaccine for.  
8
8
Human 
Immuno-
deficiency 
Virus (HIV) 
• Sex 
• Blood 
• From mother to child
HIV is passed 
from person 
to person 
through: 
There is 
currently no 
vaccine or 
cure for HIV.
However, 
treatment 
options are 
available.
Vaccine 
studies are 
on-going 
worldwide.
9
9
Why is this study being 
done?
Determine the safety of the vaccines and any 
side effects they may cause. 
Determine
Learn how they act on the body, if the body 
develops an immune response and how long 
the effects of the vaccines last. 
Learn
Compare effects of each combination of 
vaccines to each other and to placebo.
Compare
10
10
About Vaccines
A vaccine is a substance that teaches the 
body to defend itself against an infection 
(or germ).
This defensive response is called the 
immune response, and it is the body’s 
way to fight infections.
Vaccines teach your immune system to 
recognize certain germs and defend you 
if you come into contact with that germ.
11
11
The vaccines in this study:
are experimental
do not contain HIV
cannot give you HIV
may not protect you from HIV
12
12


3
What vaccines are being 
tested?
Env-C Plasmid DNA
HIV Env gp145 
C.6980 protein
13
13
Adjuvants
This study also tests 3 different adjuvants 
that are mixed with the vaccines
• An adjuvant is a substance added to vaccines 
that can help to make the vaccine more 
effective by improving the immune response 
or causing the immune response to last longer 
than without the adjuvant. 
14
14
Adjuvants can make 
vaccines more effective 
These adjuvants will be mixed with 
the vaccines in different combinations:
• ALF43
• Rehydragel® 
• dmLT
15
15
Eligibility
Some of the reasons you might be 
eligible:
q Between 18 and 40 years old
q Healthy 
q Able to provide consent 
q Low risk for HIV infection
q Agree to use reliable contraception
q Not pregnant, breast-feeding or 
planning to become pregnant
16
16
Eligibility
Some of the reasons why you would 
not be eligible:
q Unwilling or unable to use effective 
contraception
q History of a severe allergic reaction 
q Had 3 or more sexual partners in the 
last 6 months
q Unable to attend all visits
q Suffer from a serious illness
q Unable to provide written consent
17
17
Study 
Overview
126 healthy men 
and women, 
18-40 years old
Just over 2 years 
long
26 + clinic visits  
6 vaccines
Optional samples
18
18


4
Study Visits
Screening 
Visit:
• Study Info 
and Eligibility 
Check
Vaccine 
Visits:
• 6 Vaccine 
Visits
Follow-up 
Visits:
• Heath and 
Research 
Assessments 
19
19
Screening 
Visit 
(4-5 
hours) 
q Study briefing 
q Informed consents 
q Test of understanding
q Review medical history 
q Physical exam 
q Blood draw to check your general 
health, HIV, hepatitis B, hepatitis C, 
and syphilis 
q Urine pregnancy test for women
q Urine test for general health 
q Pap smear for women who agree 
to cervicovaginal secretion collection
20
20
Vaccine 
Visits 
(4-6 
hours) 
q Physical exam & eligibility review
q Observation after vaccination
q Instructions on how to monitor 
any symptoms
q Urine pregnancy test for women
q Blood draw for research tests and 
HIV 
q There are six (6) visits where you 
will receive an experimental 
vaccine. After the first vaccine, 
vaccines will be given at 1 month, 3 
months, 5 months, 8 months and 
14 months.
21
21
Follow up Visits 
(2-3 hours)
q Brief physical exam
q Review any symptoms you may have 
experienced
q Blood draw for HIV, research tests and to 
check your general health
We will call you after each vaccination so we 
need to have a number where we can reach you. 
It is very important to tell us how you are 
doing.  If we have trouble contacting you, we 
may need to come to your house.
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Optional Specimens
You can choose to participate in the following 
additional optional collections: 
q Cervicovaginal secretion collections (women)
q Semen collections (men)
q Rectal secretion collections
q Lymph node biopsies
These collections will be explained to you in detail in 
a separate informed consent form.  You will have the 
opportunity to ask any questions about these 
collections.  You will not need to say yes to them to 
enroll in the study and you can change your mind at 
any time.
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If you are found to be qualified to 
participate in the study, you will be 
booked to come for an appointment 
for enrollment and you will be 
selected by chance to one of the 
seven (7) study groups. 
The group that you are in is 
randomly selected and neither you 
nor your study doctor will know 
which group you are in.  
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5
Study Groups
Group
Vaccines 1, 2 and 3
Vaccines 4, 5, and 6
1
Env-C Plasmid DNA IM
HIV Env gp145 C.6980/Rehydragel® IM
2
Env-C Plasmid DNA IM
HIV Env gp145 C.6980/ALF43/Rehydragel® IM
3
Env-C Plasmid DNA IM + dmLT 
TCI
HIV Env gp145 C.6980/Rehydragel® IM
4
Env-C Plasmid DNA IM + dmLT 
TCI
HIV Env gp145 C.6980/ALF43/Rehydragel® IM
5
Env-C Plasmid DNA/ALF43 IM
HIV Env gp145 C.6980/Rehydragel® IM
6
Env-C Plasmid DNA/ALF43 IM
HIV Env gp145 C.6980/ALF43/Rehydragel® IM
7
Env-C Plasmid DNA/HIV Env 
gp145 C.6980/ALF43 IM
Env-C Plasmid DNA/HIV Env gp145 
C.6980/ALF43/Rehydragel® IM
IM= intramuscular (injected in the muscle), TCI = transcutaneous application 
(applied to the skin)
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Duration
You will be asked to 
complete at least 26 
clinic visits over 2 
years and 2 months
In addition, you will be 
asked to be available 
for phone contact 
once per week for 
three weeks.
Are you available?
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26
Risks:
Blood 
draws
There is a blood draw at each 
visit. 
Blood draws can, at times, cause 
bruising, pain, or fainting. They 
rarely can cause an infection.  
The blood amounts are different at 
each visit and range from 1 TBSP 
(tablespoon) to 12 TBSP.  
Remember to drink plenty of water 
before clinic visits
27
27
Risks:
Experimental 
Vaccines
You are one of the first humans to receive 
this combination of vaccines and 
adjuvants and so not all of the side effects 
are known. 
Common expected symptoms of all 
vaccines are: fever, chills, rashes, aches 
and pains, nausea, headache, dizziness, 
and feeling tired.
Frequently, vaccines cause pain and 
swelling where you get the injection (your 
arm). 
Most people are still able to do their daily 
activities after getting a vaccine. 
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28
Risks:
More Info 
About 
Experimental 
Vaccines
Rarely, a vaccine causes a serious allergic 
reaction soon after you get the injection.  
This reaction can be a rash, hives, or 
difficulty breathing.  Tell the study staff if 
you have ever had a bad reaction to an 
injection or a vaccine.  We will monitor 
you in the clinic for at least 30 minutes 
after each vaccine and we have 
emergency staff, equipment and 
medications here, if needed. 
Some participants will  get a 
Transcutaneous Immunization skin patch 
(TCI) placed over the injection site like a 
bandage.  
The TCI bandage may cause itching, mild 
redness or rash, and changes in 
pigmentation at the site of patch 
application.  If change in pigmentation 
occurs, it could be permanent. 
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29
Researchers may use your samples for 
genetic testing.  For example, 
researchers may do “genetic variations” 
research which looks at genes that affect 
how you fight infections to try to learn why 
some people get a disease while others 
do not. We will not notify you of the 
results of any genetic test. 
Your privacy is very important. To 
protect your identity, all study samples 
and data including genetic testing results 
will not be linked to your name and will 
not be enough to independently identify 
you as an individual.
Researchers keep your study records in a 
secure place. We do not share any 
information that could identify you. 
Complete confidentiality cannot be 
promised, but every effort will be made 
to keep the records as confidential as 
possible. 
Risks:
Genetic 
Testing 
and Your 
Privacy 
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30


6
Risks:
VISP
The HIV vaccines in this study do NOT contain the 
entire HIV virus itself and cannot cause HIV 
infection or Acquired Immune Deficiency 
Syndrome (AIDS). 
But the experimental vaccines may cause 
“vaccine-induced sero-positivity” or “VISP” so you 
may test positive for HIV when you really do not 
have HIV. 
This clinic’s HIV test can tell the difference 
between real HIV infection and VISP. For this 
reason, you should avoid all HIV testing not done 
at this clinic. You will be tested for HIV regularly 
during this study.  After this, if you would like HIV 
testing, we encourage that you return to this clinic 
for testing.
Also, if you become pregnant and have the baby 
while you have VISP, your baby may have VISP 
too.  This clinic’s HIV test can tell the difference 
between real HIV infection and VISP in your baby 
as well. 
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31
Risks:
More info 
about 
VISP
If you have VISP, you cannot donate blood. You 
must not donate blood during your participation in 
this research study for other reasons as well. You 
may also be excluded from participation in other 
research studies. At your request, you will be 
provided with a letter explaining your participation 
in the study and the possibility of testing positive 
for HIV antibody.  
We do not know how long you will have VISP. 
If you have problems because of VISP, tell the 
study staff and they will assist you. 
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32
Risks:
Possible 
Social 
Issues 
If you join this study:
§ Your family or partner might worry or treat you 
badly
§ You could lose your job 
§ You may feel embarrassed 
§ You may feel anxious when waiting for your HIV 
test results
§ Your samples and information (data) may be 
accidentally released
Researchers and study staff try hard to protect you 
and have a duty to maintain your privacy.  
But there is a risk that others, including your 
partner, may find out that you are participating in 
this study. They may misunderstand and think you 
have HIV.
If you have any of these problems, please talk to 
the study staff,  so that they can try to help you.
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33
Risks:
Pregnancy 
and Breast-
feeding
You should not become pregnant 
during this study. Researchers do not 
know if the vaccines may harm unborn 
babies. 
Use effective contraception beginning 
45 days prior to the first vaccination and 
continuing through 90 days after the last 
vaccine/placebo visit.
You must not breastfeed while in this 
study. Researchers do not know if the 
vaccines may pass through breast-milk 
and may harm your baby. 
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HIV Infection Risk
These experimental HIV vaccines have not 
shown that they work to protect against 
HIV infection. 
None of the experimental HIV vaccine 
combinations in this study have been 
shown to protect against HIV infection. 
There is also a possibility that you may be 
assigned to receive the inactive placebo.
You MUST continue to use all 
precautions to protect yourself 
from HIV. 
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35
Your Choices
Participation in this study is 100% 
voluntary
You may choose opt in or out of:
q Genetic testing 
q Sample storage for future research
q Optional sample collections
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7
Your Rights
You can change your mind at any time. We do ask that 
you tell the study staff if you are thinking about leaving or 
have decided to leave this study.  We will be very 
concerned if you “disappear”, but we will not be angry 
with you.
Study staff may want you to do some follow up visits and 
testing before you leave this study. 
Any care that you get at this clinic outside of this study 
will not change.
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37
Reimbursement
You will need to spend some time and maybe some money to 
participate in this study and researchers will reimburse you for 
some of these expenses.
Reimbursement amounts:
Study visit:  
1000 Ksh
Unscheduled visit:  
Up to 500 Ksh
*Secretion collection:  
1000 Ksh
*Lymph node biopsy: 
5000 Ksh
Transportation: 
Up to 3000 Ksh
* optional
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Thank for your time, interest and attention!
Ask questions at any time, now or in private later.
Please take all the time you need to decide to 
participate or not.
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RV460 / WRAIR #2672 
 
Version 4.0 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
17 May 2021 
________________________________________________________________________________________________________ 
Page 202 of  204 
ATTACHMENT 1: COVID INFORMATION SHEET  


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
Version 1.0  
04 August 2020 
  COVID-19 Information Sheet 
Page 1 of 2 
 
 
Kenya Medical Research Institute (KEMRI)  
United States Army Medical Research Directorate-Africa (USAMRD-A) 
In Collaboration with 
US Military HIV Research Program (MHRP) and the 
US Department of Defense (DoD) 
 
WRAIR #2672/RV460 Information Sheet for COVID-19  
 
In light of the circulating severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) and 
the associated coronavirus disease (COVID-19) pandemic, we want you to know that coming to 
the clinic and being around other people can increase your exposure to SARS-CoV-2.     
In order to reduce your risk of contracting the virus, KEMRI/WRP CRC is practicing COVID-19 
control measures like social distancing, handwashing, wearing masks and taking temperatures of 
all persons entering the institution at the entrance. 
In the event that there is an increase in infections that would prompt the need to modify study 
visits to reduce the risk of transmission, the site may institute the following modifications. 
• Visit windows may be extended in order to conduct study visits early or late within the 
window 
• Ability to conduct study visits – in full or in part – off-site if permitted by applicable 
government, health authority, and institutional policies 
• Certain study procedures may be prioritized during a particular visit so that the 
participant does not have to be present for the full duration of the scheduled study visit. 
Other modifications may be undertaken that are not listed above.  However, any proposed 
modifications put in place are to safeguard the health and well-being of participants. The 
modifications provide flexibility for conducting study visits and procedures when needed to 
monitor your safety. 
These modifications are expected to be time-limited in relation to the COVID-19 pandemic. In 
consultation with the Sponsor and MHRP, the study team will determine when, in the future, the 
guidance is no longer applicable. WRAIR and the local IRBs/ECs will be notified when such a 
determination is made. 
If you should have any questions or concerns about coming to the clinic and/or continuing with 
the study, please contact 
 
Dr. Josphat Kosgei, 
MBCHB, MSc  
 
Office: 
(0)5220 36302 
 
Mobile:  
(0)729 110 122 
 
Staff:  
(0) 5220) 36000/100 
 


RV460 / WRAIR #2672 
 
Short title: Comparative Adjuvant Study for Env-C DNA and Protein Vaccines in Kenya 
 
Version 1.0  
04 August 2020 
  COVID-19 Information Sheet 
Page 2 of 2 
If you consent, please read and then sign below. 
This form will be attached to the consent form you initially signed.   If you choose to continue 
participating in the RV 460 study, please read and then sign below.  If you still have questions, 
please ask the study doctor or one of the study staff, before signing this form.  You will receive a 
copy of this signed Participant Information Form. 
Agreement to continue taking part in the study 
• I have read this information. 
• It has been written in a language that I can read and understand.   
• The information regarding COVID-19 risk for this study has been explained to me. 
• All my questions about how the site is managing the risks associated with COVID-19 
during study participation have been answered to my satisfaction. 
 
 
 
 
Printed Name of Participant in full 
 
 
 
 
Signature of Participant 
Date (dd-MON-yyyy) 
 
 
 
_______________________________________ 
Printed Name of Person Obtaining Consent 
 
  
______________________________________ 
_____________________ 
Signature of Person Obtaining Consent 
Date (dd-MON-yyyy) 
 

SAP_001.pdf: