A Phase 1 Placebo-controlled Clinical Trial to Evaluate the Safety and Immunogenicity of SAAVI DNA-C2 Vaccine Boosted by SAAVI MVA-C Vaccine, in HIV Uninfected Healthy Vaccinia Naive Adult Participants in South Africa and the United States
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 48
- Locations
- 4
- Primary Endpoint
- Signs and symptoms of local and systemic reactogenicity, laboratory measures of safety, and adverse events
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety of and immune response to an experimental DNA HIV vaccine followed by boosting with an experimental modified vaccinia HIV vaccine (MVA) in HIV uninfected adults.
Detailed Description
The worldwide 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) and the National Institute of Allergy and Infectious Diseases (NIAID) are evaluating two subtype C HIV vaccines, SAAVI DNA-C2 and SAAVI MVA-C through this study . These two vaccines will be used together in a prime-boost regimen. The SAAVI DNA-C2 vaccine is a multigene 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 MVA vaccine expressing the same immunogens as the SAAVI DNA-C2 vaccine. MVA is a highly attenuated vaccinia virus. The purpose of this study is to evaluate the safety and immunogenicity of an experimental DNA HIV vaccine, SAAVI DNA C2, followed by boosting with an experimental recombinant MVA HIV vaccine, SAAVI MVA-C, in HIV uninfected adults. Participants will actively participate in this study for 12 months and will then be contacted and asked questions about their health once annually for 3 years following initial study injection. Participants will be randomly assigned to receive either the SAAVI prime-boost preventive vaccine regimen or placebo. Vaccination with the SAAVI DNA-C2 vaccine will occur at Months 0, 1, and 2; boost vaccinations with the SAAVI MVA-C vaccine will occur at Months 4 and 5. Additional study visits will occur at Weeks 2, 6, 10, 16, 18, and 20 and Days 147, 154, 273, and 364. 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Laboratory test results within specified ranges \[complete blood count, chemistries, cardiac troponin T, urinalysis\]
- •Good general health
- •HIV-1 and -2 uninfected
- •Have access to a participating HIV Vaccine Trials Unit (HVTU) and willing to be followed for the duration of the study
- •Willing to receive HIV test results
- •Negative hepatitis B surface antigen
- •Negative hepatitis C virus (HCV) antibodies OR negative HCV PCR if anti-HCV test is positive
- •Willing to use acceptable forms of contraception from at least 21 days prior to enrollment through the duration of the study
Exclusion Criteria
- •History of vaccination against smallpox
- •HIV vaccines in prior HIV vaccine trial
- •Immunosuppressive medications within 168 days prior to first study vaccination
- •Blood products within 120 days prior to first study vaccination
- •Immunoglobulin within 60 days prior to first study vaccination
- •Live attenuated vaccines within 30 days prior to first study vaccination or scheduled within 14 days after other vaccination (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever; influenza vaccine in nasal form)
- •Investigational research agents within 30 days prior to first study vaccination
- •Any vaccines that are not live attenuated vaccines within 14 days prior to first study vaccination
- •Allergy treatment with antigen injections within 30 days prior to first vaccination or scheduled within 14 days after vaccination
- •Received investigational research agents within 30 days prior to first vaccination
Outcomes
Primary Outcomes
Signs and symptoms of local and systemic reactogenicity, laboratory measures of safety, and adverse events
Time Frame: Measured throughout study
Secondary Outcomes
- T-cell responses as detected by HIV-1 specific interferon-gamma/interleukin-2 intracellular cytokine staining(Measured 2 weeks following the fourth and fifth vaccinations)
- HIV-1-specific neutralizing and binding antibody assays(Measured 2 weeks following the fourth and fifth vaccinations)