title: Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine.
abstract: The adjuvant activity of a single highly purified saponin from the soap bark tree Quillaja saponaria was evaluated by using it as a component in an experimental vaccine containing rHIV-1 envelope protein (HIV-1 160D) adsorbed to alum. BALB/c mice immunized with experimental vaccine formulations containing the saponin adjuvant QS-21 produced significantly higher titers of antibodies than mice vaccinated with only the alum-adsorbed HIV-1 160D. Potent amnestic antibody responses to HIV-1 viral proteins were also induced. Ag-specific proliferative responses to recombinant proteins and to three variants of HIV-1 were significantly increased using QS-21 as an adjuvant. Alum-adsorbed HIV-1 160D failed to induce measurable proliferative responses to inactivated HIV-1 viruses, but group-specific proliferative responses were raised when the QS-21 adjuvant was used in the vaccine formulation. MHC class I restricted CTL specific for the immunodominant V-3 loop were induced but only when the QS-21 adjuvant was included in the vaccine formulation. The production of serine esterase by Ag-activated splenic mononuclear cells, indicating the maturation of precursor CTL, was used as a secondary measure of CTL activity, and this response was also increased. The specificity of antibody responses was not significantly broadened using QS-21; the adjuvant increased the immune recognition of epitopes throughout the HIV-1 glycoprotein 160. However, the specificity of the proliferation and serine esterase responses was broadened, suggesting that the QS-21 augmented cell-mediated immune responses specific for epitopes outside of the V-3 loop. Additionally, the QS-21 adjuvant appeared to induce recognition of weakly immunogenic epitopes that were not recognized using only alum-adsorbed HIV-1 160D. The ability of QS-21 to augment both antibody and cell-mediated immune responses suggests that this adjuvant could be a valuable component in subunit vaccines.
authors.affiliation: Cambridge Biotech Corporation, Worcester, MA 01605.
authors.forename: J Y
authors.initials: JY
authors.lastname: Wu
authors.forename: B H
authors.initials: BH
authors.lastname: Gardner
authors.forename: C I
authors.initials: CI
authors.lastname: Murphy
authors.forename: J R
authors.initials: JR
authors.lastname: Seals
authors.forename: C R
authors.initials: CR
authors.lastname: Kensil
authors.forename: J
authors.initials: J
authors.lastname: Recchia
authors.forename: G A
authors.initials: GA
authors.lastname: Beltz
authors.forename: G W
authors.initials: GW
authors.lastname: Newman
authors.forename: M J
authors.initials: MJ
authors.lastname: Newman
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D004950:Esterases / Q000096:biosynthesis; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D015483:HIV Antibodies / Q000032:analysis; D019302:HIV Envelope Protein gp160; D015497:HIV-1 / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D011498:Protein Precursors / Q000276:immunology*; D012503:Saponins / Q000494:pharmacology*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D015686:Gene Products, env; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D011498:Protein Precursors; D012503:Saponins; D014614:Vaccines, Synthetic; D004950:Esterases; C022635:serine esterase