Evaluating the Immunogenicity of the AIDSVAX B/E Vaccine and the MVA/HIV62B Vaccine in Healthy, HIV-1-Uninfected Adults Who Previously Received MVA/HIV62B in DNA/MVA or MVA/MVA Regimens in HVTN 205
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: MVA/HIV62B vaccine; AIDSVAX B/E vaccine; Placebo
Intervention description: 1×10^8 TCID50 dose to be administered as a 1 mL intramuscular (IM) injection in the deltoid; 600 mcg/mL dose to be administered as a 1 mL IM injection in the deltoid; Sodium Chloride for Injection USP, 0.9% to be administered as a 1 mL IM injection in the deltoid
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of the
      AIDSVAX B/E vaccine and the MVA/HIV62B vaccine in healthy, HIV-1-uninfected adults who
      previously received MVA/HIV62B in DNA/MVA or MVA/MVA vaccine regimens in the HVTN 205 study.
    

Eligibility criteria:

        Inclusion Criteria:

        General and Demographic Criteria:

          -  Age of 18 to 55 years

          -  Prior participation in HVTN 205 with assignment to treatment (not placebo) arm:

               1. Assigned to HVTN 205 Group 1 or Group 3, and received all 4 scheduled
                  vaccinations (2 injections of pGA2/JS7 DNA (months 0, 2) and 2 injections of
                  MVA/HIV62 (months 4, 6); OR

               2. Assigned to HVTN 205 Group 4, and received at least vaccinations 1, 2 and 4 (3
                  injections of MVA/HIV62 at months 0, 2 and 6).

          -  Access to a participating HVTN clinical research site (CRS) and willingness to be
             followed for the planned duration of the study

          -  Ability and willingness to provide informed consent

          -  Assessment of understanding: volunteer demonstrates understanding of this study;
             completes a questionnaire prior to first vaccination with verbal demonstration of
             understanding of all questionnaire items answered incorrectly

          -  Willing to be contacted 2 years following initial study injection.

          -  Agrees not to enroll in another study of an investigational research agent

          -  Good general health as shown by medical history, physical exam, and screening
             laboratory tests

        HIV-Related Criteria:

          -  Willingness to receive HIV test results

          -  Willingness to discuss HIV infection risks and amenable to HIV risk reduction
             counseling.

          -  Assessed by the clinic staff as being at "low risk" for HIV infection and committed to
             maintaining behavior consistent with low risk of HIV exposure through the last
             required protocol clinic visit.

        Laboratory Inclusion Values:

        Hemogram/Complete Blood Count (CBC)

          -  Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female,
             greater than or equal to 13.0 g/dL for volunteers who were born male

          -  White blood cell count equal to 3,300 to 12,000 cells/mm^3

          -  Total lymphocyte count greater than or equal to 800 cells/mm^3

          -  Remaining differential either within institutional normal range or with site physician
             approval

          -  Platelets equal to 125,000 to 550,000/mm^3

        Chemistry

          -  Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and
             alkaline phosphatase less than 1.25 times the institutional upper limit of normal;
             creatinine less than or equal to institutional upper limit of normal.

          -  Cardiac Troponin T or I (cTnT or cTnI) does not exceed the institutional upper limit
             of normal

        Virology

          -  Negative HIV-1 and -2 blood test: Participants must have a negative test result for
             HIV infection following the HVTN Lab Program's in-study HIV testing algorithm, prior
             to initial enrollment.

          -  Negative hepatitis B surface antigen (HBsAg)

          -  Negative anti-hepatitis C virus Ab (anti-HCV), or negative HCV polymerase chain
             reaction (PCR) if the anti-HCV is positive

        Urine

          -  Normal urine:

               -  Negative urine glucose, and

               -  Negative or trace urine protein, and

               -  Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a
                  microscopic urinalysis with red blood cells levels within institutional normal
                  range).

        Reproductive Status

          -  Volunteers who were born female: negative serum or urine beta human chorionic
             gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of
             initial vaccination. Persons who are NOT of reproductive potential due to having
             undergone total hysterectomy or bilateral oophorectomy (verified by medical records),
             are not required to undergo pregnancy testing.

          -  Reproductive status: A volunteer who was born female must:

               -  Agree to consistently use effective contraception (more information is available
                  in the protocol) for sexual activity that could lead to pregnancy from at least
                  21 days prior to enrollment through the last required protocol clinic visit.
                  Effective contraception is defined as using the following methods:

               -  Condoms (male or female) with or without a spermicide,

               -  Diaphragm or cervical cap with spermicide,

               -  Intrauterine device (IUD),

               -  Hormonal contraception, or

               -  Any other contraceptive method approved by the HVTN 114 Protocol Safety Review
                  Team (PSRT)

               -  Successful vasectomy in the male partner (considered successful if a volunteer
                  reports that a male partner has [1] documentation of azoospermia by microscopy,
                  or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite
                  sexual activity postvasectomy);

               -  Or not be of reproductive potential, such as having reached menopause (no menses
                  for 1 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal
                  ligation;

               -  Or be sexually abstinent.

          -  Volunteers who were born female must also agree not to seek pregnancy through
             alternative methods, such as artificial insemination or in vitro fertilization until
             after the last required protocol clinic visit

        Exclusion Criteria:

        General

          -  Blood products received within 120 days before first vaccination

          -  Investigational research agents received within 30 days before first vaccination

          -  Body mass index (BMI) greater than or equal to 40

          -  Volunteer has 2 or more of the following cardiac risk factors:

               -  Participant report of history of elevated blood cholesterol defined as fasting
                  LDL greater than 160 mg/dL;

               -  First degree relative (eg, mother, father, brother, or sister) who had coronary
                  artery disease before the age of 50 years;

               -  Current smoker; or

               -  BMI greater than or equal to 35

          -  Pregnant or breastfeeding

          -  Active duty and reserve U.S. military personnel

        Vaccines and Other Injections

          -  Any clinically significant AE related to vaccination in HVTN 205, for which
             revaccination would be a safety concern such as any grade 3 or 4 related AE

          -  Smallpox vaccine received within the last 5 years

          -  HIV vaccine(s) received in a prior HIV vaccine trial other than HVTN 205. For HVTN 205
             participants who have subsequently received control/placebo in another HIV vaccine
             trial, the HVTN 114 PSRT will determine eligibility on a case-by-case basis.

          -  Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine
             trial. Exceptions may be made for vaccines that have subsequently undergone licensure
             by the FDA. For volunteers who have received control/placebo in an experimental
             vaccine trial, the HVTN 114 PSRT will determine eligibility on a case-by-case basis.
             For volunteers who have received an experimental vaccine(s) greater than 5 years ago,
             eligibility for enrollment will be determined by the HVTN 114 PSRT on a case-by-case
             basis.

          -  Live attenuated vaccines other than influenza vaccine received within 30 days before
             first vaccination or scheduled within 14 days after injection (eg, measles, mumps, and
             rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)

          -  Influenza vaccine or any vaccines that are not live attenuated vaccines and were
             received within 14 days prior to first vaccination (eg, tetanus, pneumococcal,
             Hepatitis A or B)

          -  Allergy treatment with antigen injections within 30 days before first vaccination or
             that are scheduled within 14 days after first vaccination

        Immune System

          -  Immunosuppressive medications received within 168 days before first vaccination. (Not
             exclusionary: [1] corticosteroid nasal spray; [2] inhaled corticosteroids; [3] topical
             corticosteroids for mild, uncomplicated dermatitis; or [4] a single course of
             oral/parenteral corticosteroids at doses less than 2 mg/kg/day and length of therapy
             less than 11 days with completion at least 30 days prior to enrollment.)

          -  Serious adverse reactions to vaccines or to vaccine components, including history of
             anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema,
             and/or abdominal pain. (Not excluded from participation: a volunteer who had a
             nonanaphylactic adverse reaction to pertussis vaccine as a child.)

          -  Hypersensitivity to eggs or egg products

          -  Immunoglobulin received within 60 days before first vaccination

          -  Autoimmune disease (eg, myositis)

          -  Immunodeficiency

        Cardiac

          -  History of myocarditis, pericarditis, cardiomyopathy, congestive heart failure with
             permanent sequelae, clinically significant arrhythmia (including any arrhythmia
             requiring medication, treatment, or clinical follow-up)

          -  ECG with clinically significant findings, or features that would interfere with the
             assessment of myo/pericarditis, as determined by a contract ECG Lab or cardiologist,
             including any of the following: (1) conduction disturbance (complete left or complete
             right bundle branch block or nonspecific intraventricular conduction disturbance with
             QRS greater than or equal to 120 ms, PR interval greater than or equal to 220ms, any
             2nd or 3rd degree AV block, or QTc prolongation (greater than 450ms)); (2)
             repolarization (ST segment or T wave) abnormality that will interfere with the
             assessment of myo/pericarditis; (3) significant atrial or ventricular arrhythmia; (4)
             frequent atrial or ventricular ectopy (eg, frequent premature atrial contractions, 2
             premature ventricular contractions in a row); (5) ST elevation consistent with
             ischemia; (6) evidence of past or evolving myocardial infarction

        Clinically Significant Medical Conditions

          -  Untreated or incompletely treated syphilis infection

          -  Clinically significant medical condition, physical examination findings, clinically
             significant abnormal laboratory results, or past medical history with clinically
             significant implications for current health. A clinically significant condition or
             process includes but is not limited to:

               -  A process that would affect the immune response,

               -  A process that would require medication that affects the immune response,

               -  Any contraindication to repeated injections or blood draws,

               -  A condition that requires active medical intervention or monitoring to avert
                  grave danger to the volunteer's health or well-being during the study period,

               -  A condition or process for which signs or symptoms could be confused with
                  reactions to vaccine, or

               -  Any condition specifically listed among the exclusion criteria below.

          -  Any medical, psychiatric, occupational, or other condition that, in the judgment of
             the investigator, would interfere with, or serve as a contraindication to, protocol
             adherence, assessment of safety or reactogenicity, or a volunteer's ability to give
             informed consent

          -  Psychiatric condition that precludes compliance with the protocol. Specifically
             excluded are persons with psychoses within the past 3 years, ongoing risk for suicide,
             or history of suicide attempt or gesture within the past 3 years.

          -  Current anti-tuberculosis (TB) prophylaxis or therapy

          -  Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as
             defined in the most recent National Asthma Education and Prevention Program (NAEPP)
             Expert Panel report).

               -  Exclude a volunteer who:

               -  Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or

               -  Uses moderate/high dose inhaled corticosteroids, or

               -  In the past year has either of the following:

               -  Greater than 1 exacerbation of symptoms treated with oral/parenteral
                  corticosteroids;

               -  Needed emergency care, urgent care, hospitalization, or intubation for asthma.

          -  Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not
             excluded: history of isolated gestational diabetes.)

          -  Thyroidectomy, or thyroid disease requiring medication during the last 12 months

          -  Hypertension:

               -  If a person has been found to have elevated blood pressure or hypertension during
                  screening or previously, exclude for blood pressure that is not well controlled.
                  Well-controlled blood pressure is defined as consistently less than or equal to
                  140 mm Hg systolic and less than or equal to 90 mm Hg diastolic, with or without
                  medication, with only isolated, brief instances of higher readings, which must be
                  less than or equal to 150 mm Hg systolic and less than or equal to 100 mm Hg
                  diastolic. For these volunteers, blood pressure must be less than or equal to 140
                  mm Hg systolic and less than or equal to 90 mm Hg diastolic at enrollment.

               -  If a person has NOT been found to have elevated blood pressure or hypertension
                  during screening or previously, exclude for systolic blood pressure greater than
                  or equal to 150 mm Hg at enrollment or diastolic blood pressure greater than or
                  equal to 100 mm Hg at enrollment.

          -  Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or
             platelet disorder requiring special precautions)

          -  Malignancy (Not excluded from participation: Volunteer who has had malignancy excised
             surgically and who, in the investigator's estimation, has a reasonable assurance of
             sustained cure, or who is unlikely to experience recurrence of malignancy during the
             period of the study)

          -  Seizure disorder: History of seizure(s) within past 3 years. Also exclude if volunteer
             has used medications in order to prevent or treat seizure(s) at any time within the
             past 3 years.

          -  Asplenia: any condition resulting in the absence of a functional spleen

          -  History of hereditary angioedema, acquired angioedema, or idiopathic angioedema.