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Background:  Recombinant viral vectors can elicit CMI responses, but immunity to the vector limits their immunogenicity.  The use of a heterologous prime-boosting regimen is one potential strategy to circumvent this problem. CMI response in animals primed with an adenovirus vector can be efficiently boosted with a poxvirus vector. To test this strategy in humans, subjects previously primed with an adenovirus vector were boosted with a poxvirus vector.

Methods: A randomized, double-blind, comparative multicenter study involving 135 subjects who had previously participated in Merck Protocol 007 (Ad5 HIV-1 gag) or Protocol 012 (MRKAd5 HIV-1 gag).  Subjects who received placebo in the parent study received ALVAC-HIV (vCP205).  Subjects who received the adenovirus vector in the parent study were randomized at a 3:1 ratio to receive ALVAC-HIV (vCP205) or MRKAd5 HIV 1 gag vaccine. Subjects were pre-stratified at entry based on their ELISPOT responses in the parent study. The primary immunogenicity assessment was the difference in the geometric mean ELISPOTs between treatment groups 4 weeks after the study vaccination.

Results:  Both vaccines were generally safe and well tolerated.  Recall responses were elicited by both vaccines.  There was no significant difference in the proportion of responders or the magnitude of the ELISPOT responses between the treatment groups.  Responses in individual subjects were consistent with the overall response in the treatment groups.

ALVAC-HIV vCP205 vs. MRKAd5 gag 15mer ELISPOT Summaries

Conclusions:    The heterologous adenovirus prime/poxvirus boost regimen was generally safe and well tolerated.  Boosting adenovirus vector-primed subjects with a poxvirus vector elicited recall CMI responses, but this was not more effective than boosting with a homologous vector.

Keywords: Vaccines; Cell mediated immunity; Prime-boost