VACCINE-INDUCED VIRUS-NEUTRALIZING ANTIBODIES AND CYTOTOXIC T-CELLS DO NOT PROTECT MACAQUES FROM EXPERIMENTAL-INFECTION WITH SIMIAN IMMUNODEFICIENCY VIRUS SIVMAC32H (J5)

To gain further insight into the ability of subunit vaccines to protec t monkeys from experimental infection with simian immunodeficiency vir us (SIV), two groups of cynomolgus macaques were immunized with either recombinant STVmac32H-derived envelope glycoproteins (Env) incorporat ed into immune-stimulating complexes (iscoms) (group A) or with these SIV Env iscoms in combination with p27(gag) iscoms and three Nef lipop eptides (group B). Four monkeys immunized with recombinant feline immu nodeficiency virus Env iscoms served as controls (group C). Animals we re immunized intramuscularly at weeks 0, 4, 10, and 16. Two weeks afte r the last immunization, monkeys were challenged intravenously with 50 monkey 50% infectious doses of virus derived from the J5 molecular cl one of SIVmac32H propagated in monkey peripheral blood mononuclear cel ls. High titers of SIV-neutralizing antibodies were induced in the mon keys of groups A and B. In addition, p27(gag)-specific antibodies were detected in the monkeys of group B, Vaccine-induced cytotoxic-T-lymph ocyte precursors against Env, Gag, and Nef were detected on the day of challenge in the monkeys of group B, Env-specific cytotoxic-T-lymphoc yte precursors were detected in one monkey from group A. In spite of t he observed antibody and T-cell responses, none of the monkeys was pro tected from experimental infection. In addition, longitudinal determin ation of cell-associated virus loads at weeks 2, 4, 6, 9, and 12 postc hallenge revealed no significant differences between vaccinated and co ntrol monkeys. These findings illustrate the need to clarify the roles of the different arms of the immune system in conferring protection a gainst primate lentivirus infections.