RECOMBINANT SUBUNIT VACCINES AS AN APPROACH TO STUDY CORRELATES OF PROTECTION AGAINST PRIMATE LENTIVIRUS INFECTION

Using pathogenic simian immunodeficiency virus (SIV) infection of maca ques as a model, we explored the limits of the protective immunity eli cited by recombinant subunit vaccines and examined factors that affect their efficacy. Envelope gp160 vaccines, when used in a live recombin ant virus-priming and subunit-protein-boosting regimen, protected maca ques against a low-dose, intravenous infection by a cloned homologous virus SIVmne E11S. The same regimen was also effective against intrare ctal challenge by the same virus and against intravenous challenge by E11S grown on primary macaque peripheral blood mononuclear cells (PBMC ). However; only limited protection was observed against uncloned SIVm ne. Priming with live recombinant virus was more effective than immuni zation with subunit gp160 alone, indicating a potential advantage of n ative antigen presentation and the possible role of cell-mediated immu nity in protection. Whole gp160 was more effective than the surface an tigen (gp130), even though both antigens elicited similar levels of ne utralizing antibodies. Animals immunized with the core (gag-pol) antig ens failed to generate any neutralizing antibody and were all infected following challenge. However, their proviral load was 10-100-fold low er than that of the control animals, indicating that immune mechanisms such as cytotoxic T lymphocytes (CTL) may play a role. Finally, anima ls immunized with both the core and the envelope antigens generated si gnificant protective immunity, even with relatively low neutralizing a ntibodies. Taken together, these results indicate that multiple mechan isms may contribute to protection. It may therefore be advantageous to incorporate multiple antigens in the design of recombinant subunit va ccines against acquired immunodeficiency syndrome (AIDS).