AEGiS-11IAC: Superinfection of HIV-2-preinfected macaques after rectal exposure to a primary isolate of SIVmac251.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Superinfection of HIV-2-preinfected macaques after rectal exposure to a primary isolate of SIVmac251.

Int Conf AIDS 1996 Jul 7-12; 11:11 (abstract no. We.A.284)
Wakrim L, Le Grand R, Vaslin B, Cheret A, Matheux F, Theodoro F, Roques P, Nicol-Jourdain I, Dormont D; Service de Neurovirologie, Commissariat a l'Energie Atomique, DRM, DSV, SSA, Fontenay-aux-Roses, France. Fax: (33-1) 46 54 77 26.

OBJECTIVES: To test the potential vaccine effect of a weakly pathogenic HIV-2 isolate against the superinfection after an intrarectal inoculation with a pathogenic SIVmac251 isolate. Method: We intrarectally challenged six HIV-2-preinfected rhesus macaques with 10 AID50 of a pathogenic isolate of SIVmac251. These monkeys have been intravenously infected with HIV-2 ROD isolate five years ago. The outcome of this atraumatic challenge was monitored by serological and virological assays. For the PCR analysis, two nested-sets of oligonucleotide primers specific for env and pol regions of SIV mac251 and two nested sets of oligonucleotide primers specific for gag and pol regions of HIV-2 ROD were used.

RESULTS: After HIV-2 inoculation, virus was isolated from all these macaques at several time points, but at the time of SIV challenge none of these HIV-2 infected animals was positive for virus isolation, p27-Gag antigenemia or HIV-2 provirus detection in PBMCs or peripheral lymph nodes. However, all monkeys exhibited anti-HIV-2 antibody titers ranging from 102 to 103. Neutralizing antibodies against the challenge SIV strain were also detected in two animals; titers were respectively 101.7 and 102. After rectal exposure to SIV mac251, five of the six HIV-2-preinfected macaques were superinfected. SIV mac251 DNA sequences were detected repeatedly in the PBMCs of the five superinfected animals and the two controls, whereas no HIV-2 provirus was detected for 14 months after challenge. Moreover, both the 5 superinfected and the control monkeys exhibited a decline in CD4+ lymphocyte cells and one superinfected macaque died 15 weeks post SIV challenge from AIDS-like disease. The one monkey that resisted superinfection was negative for all SIV infection criteria.

CONCLUSION: Intravenous inoculation of rhesus macaques with a weakly pathogenic HIV-2 isolate failed to confer protection in 5 of 6 animals against superinfection with a pathogenic closely related SIV mac251 isolate. Only one animal that exhibited the highest titers of whole IgG and cross-neutralizing anti-SIV antibodies at the day of SIV challenge was completely protected from superinfection. No protection from the progression of disease was evidenced in the 5 superinfected monkeys.

Keywords: AEGIS, HIV-2, SIV, Macaca, Simian Acquired Immunodeficiency Syndrome, Superinfection, Macaca mulatta, Acquired Immunodeficiency Syndrome, Proviruses, CD4-Positive T-Lymphocytes, Rectum, DNA Primers, Animal, ICA11

960707
WeA284