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Background:  Studies in animals have demonstrated that immunization with recombinant adenovirus vectors is an efficient way to elicit HIV-specific cell mediated immune (CMI) responses.  Two prototype recombinant Ad5 vaccines expressing a human codon optimized consensus clade B HIV-1 gag gene were tested in clinical trials.

Methods: The first vaccine, Ad5 HIV-1 gag, was tested in a multi-center, placebo controlled, randomized double blind trial in 160 healthy volunteers 18-50 years of age at low risk of HIV infection using a 3 dose regimen (Day 1, Week 4, Week 26) escalating doses from 10⁸ to 10¹¹ viral particles/dose (vp/dose).  After the study had been initiated, genetic instability in the vector was noted in later passages; therefore the vector was modified to improve stability.  The resulting vector, MRKAd5 HIV-1 gag, was tested in a multi-center, placebo controlled, randomized double blind trial in 92 healthy volunteers 18-50 years of age at low risk of HIV infection using escalating doses from 10⁹ to 10¹¹ vp/dose.  In both studies subjects were followed for safety and immunogenicity.

Results:  Both vaccines were generally safe and well tolerated.  CMI responses, as measured by ELISPOT, were elicited at all dose levels studied, though the vaccines were less immunogenic in subjects with high titers (>200) of pre-existing neutralizing antibodies to Ad5.  The dose-response relationship to immunogenicity was similar for each vaccine; therefore the data from both vaccines are combined in the table below.

Pooled Ad5 and MRKAd5 gag vaccine ELISPOT summaries at Wk 8 by Baseline Ad5 Titer

Conclusions:    In these 2 studies, both adenovirus type 5 vectors were generally safe and well tolerated and were immunogenic in humans.  Pre-existing immunity to Ad5 dampens immunogenicity.

Keywords: Vaccines; Cell mediated immunity; Adenovirus