HIV Infections
Conditions
Keywords
HIV Seronegativity, HIV Preventive Vaccine, Vaccinia vector, Pox vector
Brief 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.
Interventions
BIOLOGICALrMVA-HIV (rMVA-HIV env/gag + rMVA-HIV tat/rev/nef-RT)
rMVA 10\^7 pfu /2mL administered in each deltoid
BIOLOGICALrFPV-HIV (rFPV-HIV env/gag + rFPV-HIV tat/rev/nef-RT)
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
BIOLOGICALEmpty TBC-FPV
Empty FPV 10\^9 pfu/2mL administered as two separate 1 mL intramuscular injections, one into each deltoid.
BIOLOGICALTBC-MVA and TBC-FPV
Empty MVA 10\^7 pfu/2mL administered into each deltoid
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
Note: As of 11/29/06, vaccinations in this trial have been discontinued. Inclusion Criteria: * HIV uninfected within 8 weeks prior to first vaccination * Blood pressure 140/90 or less upon enrollment * Good general health * Willing to receive HIV test results * Understand the vaccination procedure * Negative for hepatitis B surface antigen * Negative for anti-hepatitis C virus antibodies (anti-HCV) or negative for HCV PCR if anti-HCV is positive * Willing to use acceptable forms of contraception * Willing to be followed for the duration of the study * Have access to a participating HIV vaccine trial site
Exclusion criteria
* HIV vaccines or placebos in prior HIV vaccine trial * Previously received Avipox vaccine * Previously received Vaccinia vaccine * Immunosuppressive medications within 168 days prior to first vaccination * Blood products within 120 days prior to first vaccination * Immunoglobulin within 60 days prior to first vaccination * Live attenuated vaccines within 30 days prior to first vaccination * Investigational research agents within 30 days prior to first vaccination * Medically indicated subunit or killed vaccines within 14 days prior to first study vaccine administration or allergy treatment with antigen injections within 30 days prior to first vaccination * Current tuberculosis prophylaxis or therapy * Hypersensitivity to egg products * Past or present cardiac disease * Two or more of the following cardiac risk factors: history of fasting LDL greater than 160 mg/dl; first degree relative who had heart condition, excluding hypertension; cigarette smoking * ECG with clinically significant findings (e.g., conduction disturbance, repolarization abnormality, significant atrial or ventricular arrhythmia, frequent atrial or ventricular ectopy, ST elevation consistent with ischemia, evidence of past or evolving myocardial infarction) * Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded. * Autoimmune disease or immunodeficiency * Unstable asthma * Diabetes mellitus type 1 or 2 * Thyroid disease requiring treatment * Serious angioedema within the last 3 years * Bleeding disorder * Malignancy unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period * Seizure disorder requiring medication within the past 3 years * Absence of the spleen * Mental illness that would interfere with the study * Other conditions that, in the judgment of the investigator, would interfere with the study * Pregnancy or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability, as judged by local and systemic reactogenicity signs and symptoms, laboratory measures, and adverse events | After each injection and 12 months after the first injection |
| Immunogenicity, as judged by qualitative HIV-1-specific T-cell responses | At Days 98 and 210 |
Countries
Brazil, United States
Outcome results
None listed