Evaluation of Combination DNA/Replication-Competent Ad-SIV Recombinant Immunization Regimens in Rhesus Macaques

Abstract

Combination vaccine regimens in which priming with recombinant DNA is followed by boosting with recombinant viral vectors have been shown in previous studies to effectively enhance cellular immunity. However, no information exists concerning possible synergy of the cellular immune response when DNA immunization is followed by administration of a recombinant vector able to replicate. As our approach makes use of replication-competent Ad HIV and SIV recombinants, we performed a pilot experiment in six rhesus macaques in which we compared immunogenicity resulting from priming with one or two DNA recombinants encoding the SIV_smH4 env and rev genes with that elicited by a single replication-competent Ad5hr-SIV env/rev priming immunization. All macaques were subsequently administered an Ad5hr-SIV env/rev booster immunization followed by two immunizations with SIV gp120 protein. The choice of the env gene as target immunogen allowed comparison of induced cellular immune responses as well as binding and neutralizing antibodies elicited in serum and mucosal secretions. We report here that all immunized monkeys developed strong cellular immunity to the SIV envelope as shown by secretion of interferon-γ, lysis of envelope-expressing target cells, and/or proliferation in response to gp120 or inactivated SIV. Similarly, all macaques developed anti-gp120 binding antibodies and neutralizing antibodies in serum and IgG and IgA binding antibodies in mucosal secretions. We did not observe consistently enhanced immune responses in any immunization group. We conclude that two sequential immunizations with the same replication-competent Ad5hr-SIV recombinant is as effective as priming with one or two recombinant DNA vaccines followed by a single Ad5hrSIV recombinant immunization.