Safety of and Immune Response to a DNA HIV Vaccine Boosted With a Modified Vaccinia HIV Vaccine and Protein HIV Vaccine in Healthy Adults
Condition: HIV Seronegativity; HIV Preventive Vaccine
MeSH terms: Vaccinia
Study type: Interventional
Phase: Phase 1

Summary: 
      Sub-Saharan Africa is the region most affected by the global Human Immunodeficiency Virus
      (HIV) epidemic. A vaccine is the most promising preventive approach against new HIV
      infections. The purpose of this study is to evaluate the safety and immunogenicity of 4
      experimental preventive HIV vaccine regimens in HIV-uninfected adults in South Africa.
    

Detailed description: 
      The worldwide Human Immunodeficiency Virus / Acquired Immunodeficiency Syndrome (HIV/AIDS)
      epidemic may only be controlled through development and utilization of a safe and effective
      vaccine that will prevent HIV infection. Due to the high prevalence of HIV-1 subtype C in
      southern Africa, the South African AIDS Vaccine Initiative (SAAVI), the HIV Vaccine Trials
      Network (HVTN), Novartis, and the National Institute of Allergy and Infectious Diseases
      (NIAID) are evaluating three subtype C HIV vaccines, SAAVI DNA-C2, SAAVI MVA-C, and Novartis
      Subtype C gp140 through this study. These vaccines will be used together in four prime-boost
      regimens. The SAAVI DNA-C2 vaccine is a multigene deoxyribonucleic acid (DNA) vaccine
      consisting of two DNA plasmids in equal amounts that express an HIV-1 subtype C polyprotein
      comprising of Gag-Reverse Transcriptase-Tat-Nef and an HIV-1 subtype C truncated Env. SAAVI
      MVA-C is a recombinant modified vaccinia Ankara (MVA) vaccine expressing the same immunogens
      as the SAAVI DNA-C2 vaccine. MVA is a highly attenuated vaccinia virus. The Novartis protein
      subunit vaccine is a Subtype C oligomeric V2 loop deleted glycoprotein 140 (gp140) vaccine
      (gp140[delta]V2.TV1), given with MF59 adjuvant.

      This trial is designed to build upon the Thai RV144 HIV vaccine trial, which demonstrated an
      efficacy of 31.2% among participants who received a different vaccine regimen of a pox prime
      followed by a concurrently-administered protein boost. This primary purpose of HVTN 086 is to
      evaluate the safety and immunogenicity of SAAVI DNA-C2, SAAVI MVA-C and Novartis Clade C
      gp140TV1ΔV2 with MF59 adjuvant in various vaccination regimens. The primary analysis will
      focus on a ranking strategy of the vaccine regimens that is guided by measurements of the
      immune responses elicited by these vaccines and their respective modes of delivery in various
      combinations, both sequential and concurrent.

      Participants will actively participate in this study for 12 months. Participants will be
      randomly assigned to receive either a prime-boost preventive vaccine regimen or placebo. Four
      prime-boost preventive vaccine regimens will be compared; each participant will be randomized
      to one of 4 groups. Participants in Group 1 will receive MVA-C at months 0 and 1, and
      gp140/MF59 at months 3 and 6. Group 2 will receive MVA-C and gp140/MF59 at months 1 and 3.
      Group 3 will receive DNA-C at months 0 and 1, and MVA-C at months 3 and 6. Group 4 will
      receive DNA-C at months 0 and 1, and both MVA-C and gp140/MF59 at months 3 and 6. Additional
      study visits will occur at Weeks 2, 6, 13, 14, 26, 28, 36, and 48. All participants will be
      contacted once annually for 3 years and asked questions about their health. Study procedures
      include physical exams, blood and urine collection, HIV testing, an electrocardiogram, and
      questionnaire. Some blood collected from participants will be stored and used in future
      research. Risk-reduction counseling will be conducted at all study visits.
    

Intervention name(s): MVA-C + gp140/MF59; MVA-C + gp140/MF59; DNA-C2 + MVA-C; DNA-C2 + MVA-C + gp140/MF59
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): SAAVI MVA-C administered as 0.5 ml intramuscularly in right deltoid, with placebo in left deltoid, at Month 0; SAAVI MVA-C administered as 0.5 ml intramuscularly in right deltoid at Month 1; Novartis subtype C gp140 admixed with Novartis MF59 adjuvant administered as 0.5 ml intramuscularly in left deltoid, with placebo in right deltoid, at Months 3, 6.
Placebo comparator: Placebo administered at Months 0, 1, 3, 6; SAAVI MVA-C administered as 0.5 ml intramuscularly in right deltoid, with Novartis subtype C gp140 admixed with Novartis MF59 adjuvant administered as 0.5 ml intramuscularly in left deltoid, at Months 0, 3; placebo in right deltoid at Month 1; placebo in each deltoid at Month 6
Placebo comparator: Placebo administered at Months 0, 1, 3, 6; SAAVI DNA-C2 administered as 1 ml intramuscularly in right deltoid, with placebo in left deltoid, at Month 0; SAAVI DNA-C2 administered as 1 ml intramuscularly in right deltoid at Month 1; SAAVI MVA-C administered as 0.5 ml intramuscularly in right deltoid, with placebo in left deltoid, at Months 3, 6
Placebo comparator: Placebo administered at Months 0, 1, 3, 6; SAAVI DNA-C2 administered as 1 ml intramuscularly in right deltoid, with placebo in left deltoid, at Month 0; SAAVI DNA-C2 administered as 1 ml intramuscularly in right deltoid at Month 1; SAAVI MVA-C administered as 0.5 ml intramuscularly in right deltoid at Months 3, 6; Novartis subtype C gp140 admixed with Novartis MF59 adjuvant administered as 0.5 ml intramuscularly in left deltoid, with placebo in right deltoid, at Months 3, 6
Placebo comparator: Placebo administered at Months 0, 1, 3, 6
Intervention MeSH terms: MF59 oil emulsion
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: HIV Infections; Acquired Immunodeficiency Syndrome; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases