Induction of Antigen-Specific Killer T Lymphocyte Responses Using Subunit SIV mac251 gag and env Vaccines Containing QS-21 Saponin Adjuvant

Abstract

Subunit vaccines based on recombinant proteins have proved useful for inducing antibody responses and they are safe for widespread use because they do not contain any live components. Unfortunately, they do not typically induce the types of cell-mediated immune responses required to control viral pathogens; specifically, they do not induce CD8⁺ cytotoxic T lymphocyte (CTL) responses. To increase the immunogenicity of recombinant proteins, we have used the QS-21 saponin adjuvant in subunit vaccine formulations. In the current study, experimental subunit vaccine formulations containing recombinant p55 ^gag or gp 120 ^env proteins from the mac251 strain of the simian immunodeficiency virus (SIV_mac251) and the QS-21 adjuvant were used to immunize rhesus macaques. These formulations induced SIV gag- or env-specific cellular immunity that was detectable in vitro and included killer cell activity. The induction of killer cells required prior vaccination and the responses were antigen specific for the immunogens contained in the vaccine formulations. Autologous target cells were required to detect these responses, suggesting genetic restriction, and effector cells appeared to be present in both the CD4⁺ and CD8⁺ T lymphocyte subpopulations. These data suggest that the vaccine-induced killer cell activity that was detected was mediated by both CD4⁺ and CD8⁺ lymphocytes. Despite the presence of these killer cells, all of the animals became infected with the SIV_mac251 on experimental challenge. These findings demonstrated that antigen-specific killer cell responses could be induced by a subunit vaccine formulated with the QS-21 saponin adjuvant. The characteristics of the responses suggested that the effector cells were T lymphocytes, expressing either CD4 or CD8. These data also demonstrated that these types of cellular immune responses could not protect rhesus macaques from infectious SIV_mac251 challenge.