Role of immune responses against the envelope and the core antigens of simian immunodeficiency virus SIVmne in protection against homologous cloned and uncloned virus challenge in macaques

We previously showed that envelope (gp160)-based vaccines, used in a live r ecombinant virus priming and subunit protein boosting regimen, protected ma caques against intravenous and intrarectal challenges with the homologous s imian immunodeficiency virus SIVmne clone E11S. However, the breadth of pro tection appears to be limited, since the vaccines were only partially effec tive against intravenous challenge by the uncloned SIVmne. To examine facto rs that could affect the breadth and the efficacy of this immunization appr oach, we studied (i) the effect of priming by recombinant vaccinia virus; ( ii) the role of surface antigen gp130; and (iii) the role of core antigens (Gag and Pol) in eliciting protective immunity. Results indicate that (i) p riming with recombinant vaccinia virus was more effective than subunit anti gen in eliciting protective responses; (ii) while both gp130 and gp160 elic ited similar levels of SN-specific antibodies, gp130 was not as effective a s gp160 in protection, indicating a possible role for the transmembrane pro tein in presenting functionally important epitopes; and (iii) although anim als immunized with core antigens failed to generate any neutralizing antibo dy and were infected upon challenge, their virus load was 50- to 100-fold l ower than that of the controls, suggesting the importance of cellular immun ity or other core-specific immune responses in controlling acute infection. Complete protection against intravenous infection by the pathogenic unclon ed SIVmne was achieved by immunization with both the envelope and the core antigens. These results indicate that immune responses to both antigens may contribute to protection and thus argue for the inclusion of multiple anti gens in recombinant vaccine designs.