AEGiS-11IAC: Immune responses induced by a live attenuated SIV vaccine protect against challenge with a heterologous isolate, but not variants which arise de novo in the infected animal.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Immune responses induced by a live attenuated SIV vaccine protect against challenge with a heterologous isolate, but not variants which arise de novo in the infected animal.

Int Conf AIDS 1996 Jul 7-12; 11:11 (abstract no. We.A.282)
Murphey-Corb M, Clements J, Amedee AM, Lacour N; Tulane Regional Primate Center, Covington, LA, USA. Fax: (504) 898-0329. E-mail: mickey@tmc.tulane.edu.

OBJECTIVE: To understand how conservative changes created as a result of replication of an attenuated live virus vaccine permit evasion of immune responses which protect against a more genetically diverse virus strain.

METHODS: We have previously shown that the macrophage-tropic clone, SIV/17E-Cl, serves as an excellent live attenuated vaccine by inducing immune responses by 8.5 months p.i. that protect against challenge with the heterologous primary isolate, SIV/DeltaB670 (Clements et al, 1995, J. Virol. 69:2737-2744). The nonvirulent phenotype of SIV/17E-Cl, however, is unstable, with 20% of the monkeys infected with this virus developing immunodeficiency disease after prolonged periods of clinical latency. Virulence coincides with the evolution of genetic variants identified by amino acid sequence changes in gp120. Six monkeys chronically infected for more than 2 years were further evaluated by a series of intravenous challenges.

RESULTS: 4 monkeys had normal CD4+/CD8+ lymphocyte counts, and 2 monkeys had CD4+ declines (monkeys L238 and M689) at challenge. Monkey L238 was protected at 8.5 months p.i. from challenge with SIV/DeltaB670. Following a CD4+ decline noted in this animal after 18 months p.i., a virus genetically distinct from the parental clone was cultured from PBMC (SIV/238-var). All six monkeys were initially challenged with SIV/DeltaB670. Of these, only monkey M689 became infected as evidenced by PCR of PBMC DNA and an amnestic antibody response. The five remaining animals were rechallenged with SIV/239var. Of these, monkey L238 responded with an amnestic antibody response. A second monkey, despite the fact that he was asymptomatic at challenge and was protected against challenge with SIV/DeltaB670, became infected with SIV/238var. The 3 remaining monkeys are under evaluation.

CONCLUSIONS: Immune responses induced by a live attenuated SIV vaccine protect against intravenous challenge with a heterologous isolate, but not variants which arise de novo in the infected animal. These experiments provide tools with which to understand the mechanism(s) by which SIV/HIV may evade immune responses which are protective.

Keywords: AEGIS, SIV, Vaccines, Attenuated, Macaca mulatta, Naphthalenes, Antigens, CD4, Animals, Haplorhini, Immunity, Macaca fascicularis, Immunity, Mucosal, protect, Animal, immunology, ICA11

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