AEGiS-11IAC: Protection against SIVsm in HIV-2 exposed, seronegative macaques but not in macaques exposed i.r. to subinfectious doses of SIVsm.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Protection against SIVsm in HIV-2 exposed, seronegative macaques but not in macaques exposed i.r. to subinfectious doses of SIVsm.

Int Conf AIDS 1996 Jul 7-12; 11:11 (abstract no. We.A.283)
Biberfeld G, Makitalo B, Putkonen P, Bottiger D, Rud E, Thorstensson R; Swedish Institute Of Infectious Disease Control, Stockholm, Sweden. Fax: 46-87354136.

OBJECTIVE: To study protective immunity in macaques preexposed to subinfectious doses of SIVsm or HIV-2.

METHODS: Three cynomolgus monkeys were exposed intrarectally (i.r.) to subinfectious doses of SIVsm and challenged 10 months later with 10MID50 of SIVsm i.r. Four monkeys resistant to repeated i.v. HIV-2 inoculations after passive immunization or antiviral treatment were challenged with 10MID50 of SIV i.r. 18-40 months after the last HIV-2 exposure. Virus specific humoral and cellular immune responses were investigated. Four naive control monkeys were challenged with SIV in parallel with the SIV and HIV-2 preexposed monkeys.

RESULTS: After exposure to subinfectious doses of SIV, 3 of 3 monkeys were virus isolation negative and SIV PCR negative and lacked demonstrable antibodies to SIV. However, lymphocyte proliferative responses to SIV env peptides were demonstrated in all 3 monkeys and cytotoxic T lymphocytes (CTL) to SIV gag/pol and nef proteins in 2 of 3 monkeys studied. All 3 SIV-preexposed monkeys became infected when challenged with the infectious dose of SIV. Two of the 4 HIV-2-preexposed monkeys resisted the SIV challenge as shown by negative virus isolations, negative SIV DNA PCR, lack of SIV antibodies and failure to transfer SIV with blood from the protected monkeys to naive monkeys. The 2 protected monkeys had demonstrable SIV gag/pol and nef specific CTL after SIV challenge. All 4 control monkeys became infected after SIV challenge.

CONCLUSIONS: Two of 4 monkeys repeatedly exposed to HIV-2 i.v. without becoming infected were protected against subsequent i.r. challenge with SIVsm. The presence of SIV specific CTL and lack of SIV antibodies in the protected monkeys after challenge suggest that cellular rather than humoral immunity was responsible for the protection. In contrast, all of 3 monkeys preexposed to subinfectious doses of SIV i.r. became infected after challenge with the infectious dose of SIV despite the presence of virus specific cell-mediated immunity.

Keywords: AEGIS, HIV-2, SIV, Macaca fascicularis, T-Lymphocytes, Cytotoxic, HIV-1, HIV Infections, Vaccination, Animal, ICA11

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