SAFETY AND IMMUNOGENICITY OF ENV-2-3, A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 CANDIDATE VACCINE, IN COMBINATION WITH A NOVEL ADJUVANT, MTP-PEMF59/

We investigated the safety and immunogenicity of a candidate HIV-1 vac cine, Env 2-3 (Chiron Biocine Co.), in combination with an adjuvant em ulsion, MF59, with or without an additional immune modulator, MTP-PE, in 78 healthy HIV-1-seronegative adults. Sixteen subjects participated in a dose escalation study of MTP-PE in MP59 without Env 2-3, given a t 0 and 1 months; 48 subjects participated in a study of a fixed dose of 30 mu g of Env 2-3 in MF59 with increasing doses of MTP-PE (0, 5, 1 0, 25, 50, and 100 mu g), and 14 subjects participated in a study of 1 00 mu g of Env 2-3 in MF59 without MTP-PE. Subjects were assigned to s tudy groups under a randomized, double-blind allocation. Subjects rece ived immunization at 0, 1, and 6 months, and had the option of receivi ng a fourth dose at 12-18 months. Env 2-3 in MTP-PE/MF59 was associate d with significant reactogenicity, in that severe, although self-limit ed systemic and/or local reactions occurred in 15 of 30 vaccinees. In contrast, Env 2-3 in MF59 without MTP-PE was relatively well tolerated , and severe local and/or systemic reactions occurred in only 2 of 18 subjects, Env 2-3 stimulated serum antibodies to HIV-1 envelope protei n (gp120) as detected by Western blot in 39 of 43 subjects and to HIV- 1 virus lysate by EIA in 28 of 43 subjects after three injections. The majority of subjects also developed EIA antibodies to recombinant gp1 20 (SF-2), gp120 (LAI), and V3 peptide (SF-2). Neutralizing antibodies to the homologous SF-2 strain developed in 30 of 43 and 27 of 34 subj ects, and fusion inhibition antibodies in 25 of 43 and 15 of 36 subjec ts after three and four injections, respectively, Lymphoproliferative responses to the immunogen, Env 2-3, were observed in over 80% of the vaccinees examined, and CD4+ cytotoxic T cell activity directed agains t HIV-1 was noted transiently in 2 of 20 vaccinees. Addition of MTP-PE to Env 2-3 or increasing the dose of Env 2-3 from 30 to 100 mu g did not augment immunogenicity. Env 2-3 in MF59 was well tolerated and imm unogenic in HIV-1-seronegative individuals. The addition of MTP-PE sig nificantly increased reactogenicity, but had little, if any, effect on immunogenicity.