Mj. Newman et al., INDUCTION OF ANTIGEN-SPECIFIC KILLER T-LYMPHOCYTE RESPONSES USING SUBUNIT SIVMAC251 GAG AND ENV VACCINES CONTAINING QS-21 SAPONIN ADJUVANT, AIDS research and human retroviruses, 10(7), 1994, pp. 853-861
Subunit vaccines based on recombinant proteins have proved useful for
inducing antibody responses and they are safe for widespread use becau
se 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(+) c
ytotoxic T lymphocyte (CTL) responses. To increase the immunogenicity
of recombinant proteins, we have used the QS-21 saponin adjuvant in su
bunit vaccine formulations. In the current study, experimental subunit
vaccine formulations containing recombinant p55(gag) or gp120(env) pr
oteins from the mac251 strain of the simian immunodeficiency virus (SI
Vmac251) 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 i
nduction of killer cells required prior vaccination and the responses
were antigen specific for the immunogens contained in the vaccine form
ulations. Autologous target cells were required to detect these respon
ses, suggesting genetic restriction, and effector cells appeared to be
present in both the CD4(+) and CD8(+) T lymphocyte subpopulations. Th
ese data suggest that the vaccine-induced killer cell activity that wa
s detected was mediated by both CD4(+) and CD8(+) lymphocytes. Despite
the presence of these killer cells, all of the animals became infecte
d with the SIVmac251 On experimental challenge. These findings demonst
rated that antigen-specific killer cell responses could be induced by
a subunit vaccine formulated with the QS-21 saponin adjuvant. The char
acteristics of the responses suggested that the effector cells were T
lymphocytes, expressing either CD4 or CD8. These data also demonstrate
d that these types of cellular immune responses could not protect rhes
us macaques from infectious SIVmac251 challenge.