AEGiS-11IAC: Challenge of macaques infected with a nef#-deleted SIV by the vaginal route.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Challenge of macaques infected with a nef#-deleted SIV by the vaginal route.

Int Conf AIDS 1996 Jul 7-12; 11:11 (abstract no. We.A.285)
Caufour P, Neildez O, Dilda P, Cheret A, Le Grand R, Matheux F, Theodoro F, Vaslin B, Cranage M, Dormont D; Commissariat a l'Energie Atomique, Service de Neurovirologie, DSV/DRM/SSA, BP6, Fontenay aux Roses, France. Fax: 1-46-54-77-26.

OBJECTIVE: 1) to confirm the absence of pathogenicity of a nef-deleted molecular clone (pC8) of SIVmac251 in cynomolgus macaques, 2) to assess the ability of C8 clone to protect from a vaginal challenge with a monkey-PBMC grown pathogenic isolate of SIVmac251.

METHODS: Four adult cynomolgus females, were inoculated IV with the pC8 clone which was derived from SIVmac251 (32H isolate), and was 4 amino acid deleted in the central region of Nef. Twenty months later, two of these animals and 4 controls were challenged with an SIVmac251 pathogenic isolate of SIVmac251 (10 to 100 AID50) by the vaginal route. The challenge stock was a cell-free supernatant of a primary isolate of SIVmac251 produced by macaque PBMCs. This virus stock was titrated in vivo after IV, intrarectal and intravaginal route. Virological and immunological parameters were determined by standard quantitative cell culture assays, PCR, immunoblots and ELISA.

RESULTS: Following pC8 inoculation, all animals were persistently infected. These monkeys exhibited a high humoral anti-SIV response, including neutralizing antibodies and a significantly reduced virus load when compared to monkeys infected with pathogenic SIVmac251. Unexpectedly, two macaques died at days 440 and 608 with clinical signs of AIDS, one of which presented an important fall of CD4+ cells. The two remaining animals were challenged by the vaginal route. One month post challenge, two controls and one pC8 vaccinee have biological criteria of pathogenic SIVmac251 infection. The high level of humoral anti-SIV response have been maintained in the C8 infected monkeys while the control monkeys developed normal titers of anti-SIV antibodies. In contrast, no CTL activity has been detected in any of the monkeys.

CONCLUSION: A 4 amino acid deletion in Nef seems to be not sufficient to attenuate the pathogenicity of SIVmac251 in adult macaques. Possible reversion of nef sequences of the viruses isolated from monkeys which died should be investigated. Moreover, our results seem to indicate that vaccination with attenuated virus does not protect against vaginal challenge with an homologous pathogenic virus isolate.

Keywords: AEGIS, SIV, Macaca, Polymerase Chain Reaction, Infection, Vaccination, Superinfection, Human, Female, Animal, Adult, ICA11

960707
WeA285