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Background:  The safety profile of the Merck Adenovirus Type-5- (Ad5-) based HIV vaccines was reviewed using data from phase I studies.

Methods:  Healthy adults aged 18 to 50 at low risk for HIV-infection were randomized to receive intramuscular injections of 3 x 10⁶ to 1 x 10¹¹ viral particles of a monovalent (Ad5gag or MRKAd5gag) or trivalent (MRKAd5gag/pol/nef) vaccine. Data were reviewed from all subjects who received at least 1 dose of an Ad5 vaccine. Adverse experiences were collected for 29 days after each injection using a vaccination report card with causal relationships to vaccine determined by the study investigator. Laboratory parameters were collected routinely 1 and 2 weeks following each injection, and in the trivalent study in all subjects 3 days following the first injection. The effect of baseline anti-Ad5 antibody titers on the safety profile of the vaccines was also evaluated.

Results:  Preliminary safety and tolerability data from approximately 760 subjects enrolled in phase I studies have been reviewed. The vaccines were generally well tolerated. The adverse experience profile of the monovalent and trivalent vaccines was similar. Injection site reactions (pain, swelling, erythema) were commonly observed at an overall rate of 55.1% and were similar among subjects with Ad5 titer ≤ 200 and > 200. The most common systemic adverse effectss were fatigue (22.4%), fever (14.2%), headache (43.7%), myalgia (15.7%), and rigors (11.2%). No clinically significant laboratory abnormalities were observed. In 4 subjects, 8 vaccine-related serious adverse effects were reported (transient lymphopenia [2], fatigue and chills [1], fever, cough, headache, and chest pain [1]), but no discontinuations from study occurred because of them. The majority of adverse effects were reported within 3 days after injection. The occurrence of adverse effects did not increase with subsequent doses, and the incidence of fever decreased.

Conclusions:  In these studies, the Ad5gag, MRKAd5gag, and MRKAd5trivalent vaccines were generally well tolerated and had similar safety profiles. Systemic adverse effects occurred most commonly in subjects with low pre-existing immunity to Ad5 and occurred most frequently at the 1 x 10¹¹ viral particle dose.

Keywords: vaccine; adenovirus; safety