AEGiS-11IAC: Adenovirus host range mutant-SIV recombinant vaccine trial in rhesus macaques.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Adenovirus host range mutant-SIV recombinant vaccine trial in rhesus macaques.

Int Conf AIDS 1996 Jul 7-12; 11:4 (abstract no. Mo.A.102)
Buge SL, Lubeck M, Kalyan N, Cheng S, Richardson E, Markham P, Miller C, Udem S, Robert-Guroff M; NIH, Bethesda, MD. Fax: 301-496-8394.

OBJECTIVE: To evaluate a prime-boost vaccine regimen using an adenovirus host range mutant (Ad5hr)-SIVsm envelope recombinant and native SIV251 gp120 for protective efficacy against vaginal transmission of SIV.

METHODS: Six adult female macaques were immunized orally and intranasally at 0 weeks and intratracheally at 12 weeks with Ad5hr-SIV recombinant. They were boosted at 24 weeks with syntex adjuvanted gp120. Four controls received the Ad5hr vector and syntex adjuvant; 2 controls were unimmunized. Immune responses were monitored every 2-4 weeks. T-cell proliferative responses to SIV envelope protein and peptides were assessed by thymidine incorporation and IL-2 production. Cytotoxic T-lymphocyte (CTL) activity was evaluated by Cr51-release using autologous B-cell targets infected with vaccinia-SIV env recombinants or control vaccinia. Serum antibodies were monitored by ELISA against whole disrupted SIV antigen. Antibodies in nasal and vaginal swabs were assessed by ELISA against native SIV gp120.

RESULTS: T-cell proliferative responses to SIV envelope peptides were observed sporadically in 1/6 macaques following the lst immunization and in 3/6 following the second. Significant SIV-specific CTL activity was not observed. Transient serum antibody levels to SIV envelope were first detected in all 6 immunized macaques after the 2nd immunization. Antibody levels were significantly boosted and became persistent following the gp120 inoculation. SIV-specific IgG antibodies were detected in nasal swabs of 2/6 macaques following the 2nd immunization. Following the protein boost, all 6 macaques exhibited IgG antibodies in nasal swabs and 5/6 in vaginal swabs. IgA antibodies were not observed; IgM antibodies in nasal swabs appeared in 2/6 macaques following the protein boost.

CONCLUSIONS: Ad5hr-SIV recombinant immunization and subunit boosting effectively elicited humoral and mucosal immune responses. The presence of antibodies in nasal and vaginal secretions is particularly encouraging. Following a 2nd protein boost at 36 weeks, these macaques will be challenged vaginally with SIV251 at 40 weeks (March, 1996). Results of that challenge will be reported.

Keywords: AEGIS, SAIDS Vaccines, SIV, Macaca mulatta, Adenoviridae, Macaca, Immunity, Mucosal, HIV Envelope Protein gp120, Immunoglobulin A, Immunoglobulin G, Immunization, Enzyme-Linked Immunosorbent Assay, simian immunodeficiency virus gp120, Animal, Adult, Female, immunology, ICA11

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MoA102