Safety of and Immune Response to Two HIV Vaccine Formulations (rMVA-HIV and rFPV-HIV) Alone or in Combination in HIV Uninfected Adults
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to evaluate the safety of and immune response to two HIV vaccine
      formulations, rMVA-HIV and rFPV-HIV, alone and in combination, in HIV uninfected adults.
    

Detailed description: 
      Pox viruses are used for investigational vaccines in humans because they can accommodate
      large amounts of foreign DNA, can infect mammalian cells, and can access the cytotoxic T-cell
      responses believed to be important in the control of HIV infection and disease. Two pairs of
      matching recombinant HIV vaccines have been developed for use in this study. One pair uses a
      modified vaccinia Ankara (MVA) vector and the other pair uses a fowlpox vector (FPV). Each
      vaccine pair consists of one vaccine containing env/gag sequences and one vaccine containing
      modified tat/rev/nef-RT sequences. The HIV sequences are identical and are from a vertically
      transmitted pediatric primary isolate. The controls in this study are MVA vectors and FPVs
      without the HIV genes. The study will evaluate the safety and immunogenicity of the vaccine
      pairs.

      There are two parts to this study. Participants in Part A will be randomly assigned to one of
      five different vaccination groups. Within each group, participants will be randomly assigned
      to receive either vaccine or control injections. Group 1 participants will receive the FPV
      vaccine pair or FPV control at each vaccine visit. Groups 2, 3, and 4 will receive one of
      three different doses of the MVA vaccine pair or MVA control at study entry and Month 1, then
      a fixed dose of the FPV vaccine pair or FPV control at Months 3, 5, and 7. Group 5
      participants will receive the MVA vaccine pair or MVA control at maximum tolerated dose (MTD)
      at each vaccine visit. Groups 1 and 2 will enroll simultaneously; Groups 3, 4, and 5 will
      enroll as safety data from the previous groups become available.

      In Part B, participants will be randomly assigned to receive study vaccine or control vaccine
      in one of three vaccination groups. Group 6 participants will receive the FPV vaccine pair or
      FPV control at each vaccine visit. Group 7 participants will receive the MVA vaccine pair or
      MVA control at study entry and Month 1, then a fixed dose of the FPV vaccine pair or FPV
      control at Months 3, 5, and 7. Group 8 participants will receive the MVA vaccine pair at MTD
      or MVA control at each vaccine visit. Enrollment into Groups 6, 7, and 8 will begin
      simultaneously after the completion of the safety data evaluation of Groups 1 and 2.

      Study vaccinations will be given at study entry and at Months 1, 3, 5 and 7. Tests for
      cardiac injury will be performed at screening and at each 2-week follow-up visit after
      vaccination. Participants will have an electrocardiogram (ECG) at screening and 2 weeks after
      the first and last vaccinations. Study visits will occur at screening, study entry, and at 11
      visits over 13 months. Study visits will consist of a physical exam, risk reduction/pregnancy
      prevention counseling, cardiac symptom assessment, and blood and urine collection. Women will
      have pregnancy tests at study entry and Months 1, 3, 5, 7, and 13.
    

Intervention name(s): rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT); rFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT); Empty TBC-FPV; rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT); rMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT); TBC-MVA and TBC-FPV; TBC-MVA and TBC-FPV; TBC-MVA and TBC-FPV
Intervention type(s): Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological
Intervention description(s): rMVA 10^7 pfu /2mL administered in each deltoid; Vaccines administered as two separate 1-mL intramuscular injections, with rFPV-HIV env/gag into the left deltoid, rFPV-HIV tat/rev/nef-RT into the right deltoid; Empty FPV 10^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid.; rMVA 10^8 pfu /2mL administered in each deltoid; rMVA 10^9 pfu /2mL administered in each deltoid; Empty MVA 10^7 pfu/2mL administered into each deltoid; Empty MVA 10^8 pfu/2mL administered into each deltoid; Empty MVA 10^9 pfu/2mL administered into each deltoid
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: HIV Seronegativity; HIV Preventive Vaccine; Vaccinia vector; Pox vector