INDUCTION OF NEUTRALIZING ANTIBODIES TO T-CELL LINE-ADAPTED AND PRIMARY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES WITH A PRIME-BOOST VACCINE REGIMEN IN CHIMPANZEES

Five chimpanzees were immunized by administration of one or more intra nasal priming doses ofone to three recombinant adenoviruses containing a gp160 insert from human immunodeficiency virus type 1 (HIV-1) MN (H IV-1(MN)) followed by one or more boosts of recombinant HIV-1(SF2) gp1 20 delivered intramuscularly with MF59 adjuvant, This regimen resulted in humoral immune responses in three of five animals, Humoral respons es included immunochemically active anti-HIV-1 antibodies (Abs) direct ed to recombinant gpl20 and neutralizing Abs reactive with T-cell-line -adapted HIV-1(MN) and HIV-1(SF2). In addition, neutralizing activity was detected to the two homologous primary isolates and to two of thre e heterologous primary isolates which, like the immunizing strains, ca n use CXCR4 as a coreceptor for infection, The three animals with dete ctable neutralizing Abs and a fourth exhibiting the best cytotoxic T-l ymphocyte response were protected from a low-dose intravenous challeng e with a cell-free HIV-1(SF2) primary isolate administered 4 weeks aft er the last boost. Animals were rested for 46 weeks and then rechallen ged, without a boost, with an eightfold higher challenge dose of HIV-1 (SF2). The three animals with persistent neutralizing Abs were again p rotected, These data show that a strong, long-lived protective Ab resp onse can be induced with a prime-boost regimen in chimpanzees, The dat a suggest that in chimpanzees, the presence of neutralizing Abs correl ates with protection for animals challenged intravenously with a high dose of a homologous strain of HIV-1, and they demonstrate for the fir st time the induction of neutralizing Abs to homologous and heterologo us primary isolates.