A Study of Safety, Tolerability, and Immunogenicity of the MRKAd5 Gag/Pol/Nef Vaccine in Healthy Adults (V520-016)

A Phase I Dose-Ranging Study of the Safety, Tolerability, and Immunogenicity of the Merck Trivalent Adenovirus Serotype 5 HIV-1 Gag/Pol/Nef Vaccine (MRKAd5 HIV-1 Gag/Pol/Nef) in a Prime-Boost Regimen in Healthy Adults

The goal of this study is to understand the safety, tolerability and immunogenicity of the Merck Trivalent Adenovirus Serotype 5 HIV-1 gag/pol/nef

Vaccine (MRKAd 5 HIV-1 gag/pol/nef) vaccine in healthy human volunteers compared to placebo. The study will also evaluate a number of dose levels and the necessity for and timing of booster injections.

The study will proceed in four stages. Following stages I, II and III, all subjects will have the Postdose 1 (PD1) clinical and laboratory safety data reviewed by the Safety Evaluation Committee (SEC). If these data are acceptable, the next stage will be initiated.

• In Stage I, participants will be randomized to receive 3 doses of the 3x10^9vp/dose level Trivalent vaccine or placebo.
• In Stage II, participants will be randomized to receive 2 or 3 doses of the 3x10^10vp/dose level Trivalent vaccine or placebo.
• In Stage III, participants will be randomized to receive 3 doses of the Trivalent vaccine with titers of 1x10^11vp/dose, 3x10^6vp/dose, 3x10^7vp/dose, or 3x10^8vp/dose or placebo.
• In Stage IV, participants will be randomized to all treatment groups. In addition, some participants will be randomized to an MRKAd 5 HIV-1 gag Monovalent vaccine. In this stage, participants will be pre-stratified by baseline Ad5 titers (=<200, and >200), to ensure an even distribution of participants with high and low Ad5 titers across the various treatment groups.

Inclusion Criteria:

• Subjects 18 Years to 45 Years in Stages I-III and 18 Years to 50 Years in Stage IV.
• Subject is in good general health
• Subjects of reproductive potential agree to use acceptable method of birth control through study
• Subject tests negative for Hepatitis B, Hepatitis C, and HIV

Exclusion Criteria:

• Subject has a recent history of fever at time of vaccination
• Subject has received immune globulin or blood product 3 months prior to injection
• Subject has been vaccinated with live virus vaccine 30 days prior to receipt of first dose
• Subject has been vaccinated with inactivated vaccine with 14 days prior to receipt of first dose
• Subject has a chronic medical condition that is considered progressive
• Subject has history of malignancy
• Subject weighs less than 105 lb.
• Female subject is pregnant or breast feeding, Male subject is planning to impregnate during the first year of study
• Subject has contraindication to intramuscular injection
• Subject has a tattoo on the deltoid region of the arm or the injection of Depo-Provera
• Subject is unlikely or unwilling to adhere to lower risk sex practices during the course of the study