title: Induction of antigen-specific killer T lymphocyte responses using subunit SIVmac251 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 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)
authors.affiliation: Cambridge Biotech Corporation, Worcester, Massachusetts 01605.
authors.forename: M J
authors.initials: MJ
authors.lastname: Newman
authors.forename: K J
authors.initials: KJ
authors.lastname: Munroe
authors.forename: C A
authors.initials: CA
authors.lastname: Anderson
authors.forename: C I
authors.initials: CI
authors.lastname: Murphy
authors.forename: D L
authors.initials: DL
authors.lastname: Panicali
authors.forename: J R
authors.initials: JR
authors.lastname: Seals
authors.forename: J Y
authors.initials: JY
authors.lastname: Wu
authors.forename: M S
authors.initials: MS
authors.lastname: Wyand
authors.forename: C R
authors.initials: CR
authors.lastname: Kensil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology*; D015752:Genes, env / Q000276:immunology; D015750:Genes, gag / Q000276:immunology; D008198:Lymph Nodes / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D008969:Molecular Sequence Data; D018449:SAIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D012503:Saponins / Q000008:administration & dosage* / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D014611:Vaccination
chemical_list: D018449:SAIDS Vaccines; D012503:Saponins; C078785:saponin QA-21V1