A RECOMBINANT HUMAN ADENOVIRUS EXPRESSING THE SIMIAN IMMUNODEFICIENCYVIRUS GAG ANTIGEN CAN INDUCE LONG-LIVED IMMUNE-RESPONSES IN MICE

Human adenovirus type 5 can be used as a vector to elicit immune respo nses to antigens expressed from heterologous DNA sequences incorporate d into the viral genome, for example in mice immunized intraperitoneal ly. We have used a recombinant adenovirus which expresses the p55(gag) antigen of simian immunodeficiency virus to evaluate the nature and l ongevity of the response elicited when administered to mice by alterna tive routes which translate more readily to larger animals and man. In C57Bl/6 mice immunized orally with a single dose of virus, a majority of the animals which showed evidence of responding to the immunogen b y producing an anti-adenovirus response also produced a plasma antibod y response to Gag which persisted for more than 1 year and a Gag-speci fic cytotoxic T cell response that could be detected for at least 6 mo nths. In a minority of similarly immunized responding animals, only a cytotoxic response to Gag was observed although both humoral and cellu lar responses to adenovirus antigens were seen; intranasal immunizatio n produced a Gag-specific response similar to this latter pattern. The se findings suggest that delivery of adenovirus recombinants orally or intranasally may be a useful strategy for eliciting long-term cytotox ic T cell memory responses in splenocytes to candidate vaccine antigen s.