INDUCTION OF CROSS-REACTIVE CYTOTOXIC T-LYMPHOCYTE RESPONSES SPECIFICFOR HIV-1 GP120 USING SAPONIN ADJUVANT (QS-21) SUPPLEMENTED SUBUNIT VACCINE FORMULATIONS

The antigenic variation associated with Human Immunodeficiency Virus t ype-1 (HIV-1) envelope proteins could limit their utility in vaccines if the immune responses induced are specific for immunodominant variab le epitopes. We evaluated the ability of experimental subunit vaccines , containing recombinant forms of the envelope glycoprotein (rgp120) f rom two HIV-1 variants, to induce immune responses capable of recogniz ing unrelated HIV-1 variants. A vaccine formulation based on HIV-1(III B/LAI)gp120 and supplemented with saponin adjuvant (QS-21) induced neu tralizing antibodies specific for the HIV-1(IIIB/LAI) variant. This an tibody response was presumably specific for the variable principle neu tralizing determinant (PND) of the third variable region of gp120, the V-3 region. This formulation induced cytotoxic T-lymphocytes (CTL) sp ecific for the dominant V-3 epitope but also to an additional unidenti fied epitope outside of this region. The CTL specific for this second epitope also recognized gp120 from the HIV-1(MN) and HIV-1(RF) variant s in a ''cross-reactive'' manner. A second vaccine for formulation bas ed on HIV-1(MN) rgp120 and QS-21 adjuvant induced neutralizing antibod ies that were again variant-specific but also CTL that recognized all three HIV-1 variants in a cross-reactive manner. These data demonstrat e that CTL capable of recognizing different HIV-1 variants, which are presumed to be specific for a conserved HIV-1 gp120 epitope, can be in duced using subunit vaccines with the appropriate adjuvant while varia nt-specific antibody responses are produced. These findings support fu rther evaluation of this vaccine format. (C) 1997 Elsevier Science Ltd .