Combined systemic and mucosal immunization with microsphere-encapsulated inactivated simian immunodeficiency virus elicits serum, vaginal, and tracheal antibody responses in female rhesus macaques

We determined the efficacy of immunization with microsphere encapsulated wh ole inactivated simian immunodeficiency virus (SIV) by combined systemic an d mucosal administration to protect female rhesus macaques against vaginal challenge with homologous rhesus PBMC-grown SIVmac251. Animals in one group were primed and boosted intramuscularly. Two groups were primed intramuscu larly and boosted either intratracheally or orally. A final group was prime d by vaccinia/rgp140 scarification and subdivided for either intratracheal or oral boosting. Strong ELISA titers of circulating SIV-specific IgG and m odest IgA responses were elicited in the animals primed intramuscularly. In tratracheal boosting in the intramuscularly primed macaques resulted in hig h bronchial alveolar wash (BAW) IgG and less pronounced IgA. SIV-specific v aginal wash (VW) IgG was also present in the intramuscular/intramuscular an d intramuscular/intratracheal groups. Vaccinia/rgp140 priming gave low ELIS A titers to whole SIV, and failed to elicit mucosal antibody regardless of the booster route. No animal in any group developed serum neutralizing anti body to homologous SIVmac251, On vaginal challenge none of the immunized gr oups was infected at a lesser frequency than the unimmunized controls. Thes e data suggest that the use of microspheres in a combined parenteral and mu cosal regimen is an effective method of eliciting IgG and IgA antibody at m ucosal surfaces.