Induction of Antigen-Specific Killer T Lymphocyte Responses Using Subunit SIV_mac251gagandenvVaccines 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 p55gag or gp120env proteins from the mac251 strain of the simian immunodeficiency virus (SIVmac251) 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 SIVmac251 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.(ABSTRACT TRUNCATED AT 250 WORDS)

ISCOMs: an adjuvant with multiple functions

“…This has been reported for influenzaISCOMs containing ISCOPREP 703 [14] and QS-21 formulated with OVA [112], HIV gp160 [113], HIV-1 gp160 peptides [114], recombinant human CMV glycoprotein B [115], RSV F protein [116], and ras-expressing tumor cells [117]. SIV envelope glycoprotein (Env) and p27gag protein in ISCOMs and SIV proteins formulated with QS-21 induced CTL activity in non-human primates [118,119].…”

Adjuvant-enhanced antibody responses to recombinant proteins correlates with protection of mice and monkeys to orthopoxvirus challenges

“…This effect of immunostimulatory adjuvants has been noted previously for other immunogens. Both QS-21 [54][55][56][57][58] and CpG ODNs [59,60] can also augment the production of antigen-specific cytotoxic T cells, though this was not evaluated in the present study.…”

Structural and Immunological Characterization of the Vaccine Adjuvant QS-21

“…Interestingly, QS-21 also elicited earlier seroconversion. More recently, it has been demonstrated by Newman et al (1994) that vaccination of rhesus macaques with a recombinant SIV gp120 adjuvanted with QS-21 sets up both CD4+ and CD8+ mediated CTL response (measured in PBL after in vitro stimulation with Con A, IL-2, and antigen).…”