Protection of macaques against intrarectal infection by a combination immunization regimen with recombinant simian immunodeficiency virus SIVmne gp160 vaccines

We previously reported that immunization with recombinant simian immunodefi ciency virus SIVmne envelope (gp160) vaccines protected macaques against in travenous challenge by the cloned homologous virus E11S but that this prote ction was only partially effective against the uncloned virus, SIVmne. In t he present study, we examine the protective efficacy of this immunization r egimen against infection by a mucosal route. We found that the same gp160-b ased vaccines were highly effective against intrarectal infection not only with the E11S clone but also with the uncloned SIVmne, Protection against m ucosal infection is therefore achievable by parenteral immunization with re combinant envelope vaccines. Protection appears to correlate with high leve ls of SIV-specific antibodies and, in animals protected against the unclone d virus, the presence of serum-neutralizing activities, To understand the b asis for the differential efficacies against the uncloned virus by the intr avenous versus the intrarectal routes, me examined viral sequences recovere d from the peripheral blood mononuclear cells of animals early after infect ion by both routes. We previously showed that the majority (85%) of the unc loned SIVmne challenge stock contained V1 sequences homologous to the molec ular clone from which the vaccines were made (E11S type), with the remainde r (15%) containing multiple conserved changes (the variant types). In contr ast to intravenously infected animals, from which either E11S-type or the v ariant type V1 sequences could be recovered in significant proportions, ani mals infected intrarectally had predominantly E11S-type sequences. Preferen tial transmission or amplification of the E11S-type viruses may therefore a ccount in part for the enhanced efficacy of the recombinant gp160 vaccines against the uncloned virus challenge by the intrarectal route compared with the intravenous route.