Background:  Data from phase I studies suggest that monovalent gag Adenovirus type-5 (Ad5) vaccines are generally well tolerated and immunogenic. The genetic variability of HIV and restriction of cellular immune responses by HLA may limit vaccine responses. To increase the breadth of response, we constructed an Ad5-based trivalent vaccine. This study evaluated the safety, tolerability, and immunogenicity of the MRKAd5 trivalent vaccine composed of MRKAd5gag, MRKAd5nef, and MRKAd5pol in a 1:1:1 ratio.

Methods:  Healthy adults aged 18 to 50 were randomized to receive intramuscular injections of 3 x 10⁶ to 1 x 10¹¹ viral particles of the MRKAd5 trivalent vaccine or placebo at weeks 0, 4, and 26. Subjects were followed post-vaccination. Safety was assessed using a vaccine report card and safety laboratories. Immunogenicity was evaluated by the IFN-γ ELISpot assay.

Results:  We randomized 273 people to receive MRKAd5 trivalent vaccine or placebo. The study is ongoing and preliminary data are presented. The vaccine was generally well tolerated at all doses. The most common vaccine-related adverse events observed were fatigue (8.6%), headache (17.8%), injection site reactions (34.5%), myalgia (4.0%), pyrexia (10.3%), and rigors (6.3%). Adverse effects were most common at the 1 x 10¹¹ viral particle dose. There were no vaccine-related serious adverse effects. Immunogenic responses (> 55 SFC/10⁶ PBMC and ≥ 4-fold over media control) were observed at doses ≥3x  10⁹ viral particles. Immunogencity data were available for the majority of subjects at weeks 4 and 8.

Conclusions:  Preliminary safety data suggest the MRKAd5 trivalent vaccine was generally safe and well tolerated at all doses studied. Adverse effects occurred most frequently at the 1 x 10¹¹ viral particle dose. Preliminary immunogenicity data suggest that the MRKAd5 trivalent vaccine was immunogenic eliciting responses against the 3 antigens included in the vaccine.

Keywords: Vaccine; Adenovirus; Cell-Mediated Immunity