Some vaccines may work better when given together with another substance known as an adjuvant or when given with an experimental procedure called electroporation (EP). EP is a method where an electric pulse is administered to the same muscle where the vaccine injection is given. The addition of the adjuvant to the vaccine and the delivery with EP may increase a person's immune response to the vaccine. Combination approaches such as a DNA vaccine followed by live vector boost may also increase a person's immune response to the vaccine components. All of these interventions will be tested in this study. This study will evaluate the safety and tolerability of and immune response to an HIV DNA vaccine with or without plasmid IL-12 adjuvant, when given by EP and followed by a live vector vaccine given IM by needle and syringe in healthy, HIV-uninfected adults.
The effectiveness of a vaccine may be increased when combined with an adjuvant and/or when given with EP. The addition of an adjuvant or EP may increase a person's immune response to a vaccine. Furthermore, the immune response to HIV antigens may be improved by giving a DNA vaccine boosted with a live vector vaccine. The purpose of this study is to evaluate the safety, tolerability, and immunogenicity of an HIV DNA vaccine (HIV-MAG) alone or in combination with an IL-12 pDNA adjuvant, delivered IM via EP followed by a Vesicular Stomatitis Virus (VSV) HIV gag vaccine boost given IM by needle and syringe in healthy, HIV-uninfected adults. Participants will be enrolled into the study in one of four groups. Each of the four groups will receive 3 mg of the HIV-MAG vaccine alone or combined with one of three different doses of the IL-12 pDNA adjuvant, followed by the VSV HIV gag vaccine boost. Within each of the four groups, participants will be randomly assigned to receive the study vaccines or placebo. At study entry (Day 0), all participants will undergo a physical examination and blood collection. Female participants will also take a pregnancy test. Participants will complete questionnaires and receive counseling on HIV risk reduction. They will also receive their first vaccination. Participants will remain in the clinic for 30 minutes after the vaccination for observation and monitoring. Additional vaccination study visits will occur at Months 1, 3, and 6. At Months 1 and 3, participants will receive the same vaccine or placebo they received at study entry; at Month 6, participants will receive the VSV HIV gag vaccine or placebo. For 3 days after the study entry and Months 1 and 3 vaccination visits, participants will record their symptoms in a diary. After the Month 6 vaccination visit, participants will record their symptoms for 7 days. Participants in Groups 1 and 3 will attend additional study visits on Days 1, 3, 14, 42, 91, 98, 169, 171, 175, 182, 273, and 364. Participants in Groups 2 and 4 will attend additional study visits on Days 14, 42, 98, 182, 273, and 364. Most study visits will include a physical examination, blood collection, oral mucosa examination, interviews and questionnaires, and oral mucosa examination. If participant has any oral sores, oral swabs may be collected. Saliva also may be collected. Select study visits will include a mini mental state exam, urine collection, HIV testing, and risk reduction counseling. Study researchers will contact participants at Months 15, 24, and 36 for follow-up health monitoring.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
100
Participants assigned to receive the HIV-MAG vaccine will receive 3 mg of the vaccine with bupivacaine, alone or admixed with one of three doses of the IL-12 pDNA adjuvant.
Participants assigned to receive the IL-12 plasmid (IL-12 pDNA) adjuvant will receive one of three doses (total of 250 mcg, 1000 mcg, or 1500 mcg) of the adjuvant admixed with the HIV-MAG vaccine.
Participants assigned to receive the VSV HIV gag vaccine will receive a total dose of 1x10\^8 plaque-forming units (PFUs) administered as 5x10\^7 PFU in 1 mL by IM injection in both the left and right deltoids at Month 6.
Placebo will consist of sodium chloride for injection, USP 0.9%.
The HIV-MAG vaccine, IL-12 pDNA adjuvant, and placebos for IL-12 pDNA adjuvant/HIV-MAG vaccines will be delivered IM into the deltoid by the Ichor Medical Systems TDS EP device.
Columbia P&S CRS
New York, New York, United States
New York Blood Center CRS
New York, New York, United States
University of Rochester Vaccines to Prevent HIV Infection CRS
Rochester, New York, United States
Penn Prevention CRS
Philadelphia, Pennsylvania, United States
Vanderbilt Vaccine (VV) CRS
Nashville, Tennessee, United States
Frequency and severity of local injection/EP site reactogenicity signs and symptoms
Pain, tenderness, erythema, induration, and maximum severity of pain and/or tenderness
Time frame: Measured through Month 12
Frequency and severity of systemic reactogenicity signs and symptoms
Fever, malaise/fatigue, myalgia, headache, nausea, vomiting, chills, arthralgia, and maximum severity of systemic symptoms
Time frame: Measured through Month 12
Magnitude of local injection/EP site pain as measured by a visual analog scale
Time frame: Measured through Month 12
Frequency of adverse events (AEs) categorized by MedDRA body system, MedDRA preferred term, severity, and assessed relationship to study products
Detailed description of all AEs meeting DAIDS criteria for expedited reporting
Time frame: Measured through Month 12
Distribution of values of safety laboratory measures
White blood cells, neutrophils, lymphocytes, hemoglobin, alkaline phosphatase, platelets, alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and creatine phosphokinase (CPK) at baseline and at follow-up visits postvaccination
Time frame: Measured through Month 12
Number of participants with early discontinuation of vaccinations and reason for discontinuation
Time frame: Measured through Month 12
Distribution of responses to questions regarding acceptability of study injections procedures
Time frame: Measured through Month 12
Response rate of CD4 T-cell responses measured by intracellular cytokine staining (ICS) for IFN-γ and/or IL-2, to HIV potential T-cell epitope (PTE) peptide pools representing Gag, Pol, Env, Nef, Tat, and Vif
Time frame: Measured through Month 12
Response rate of CD8 T-cell responses measured by ICS for IFN-γ and/or IL-2, to HIV PTE peptide pools representing Gag, Pol, Env, Nef, Tat, and Vif
Time frame: Measured through Month 12
Response rate of T-cell responses as measured by IFN-γ enzyme-linked immunospot (ELISpot)
Time frame: Measured through Month 12
Induction of binding antibodies to HIV-1 gag p55 and HIV-1 6101 env gp160
Time frame: Measured through Month 12
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