DEVELOPMENT OF A MONKEY MODEL FOR TESTING ANTIVIRAL AGENTS AGAINST HIV-1

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A good animal model for HIV-1 is essential for AIDS vaccine studies and development of efficacious anti-viral agents. Pig-tailed macaques have been found to be susceptible to HIV-1 infection (Agy, et al., 1992). Based upon this initial report, we previously infected 2 pig-tailed macaques (designated as PT86 and PT99) with HIV-1/LAI and have monitored long-term infection and clinical changes. Each animal responded uniquely to the infection. In the case of PT86 viral sequences (DNA and RNA) were detected in the PBMC in the first year whereas the lymph nodes were positive even at 3 years P.I. Antibodies to HIV-1 gag and env proteins have persisted in PT86. The CD4+/CD8+ ratio continues to gradually decline. In the case of PT99 viral DNA sequences were seen in the PBMCs upto 1 year and in the lymph node 3 years PI. Antibodies to the env proteins have persisted. No clinical symptoms have thusfar developed in PT86 or PT99. Since the clinical symptoms of AIDS in humans generally develop in 5-10 years and developed after about 10 years post-infection in one chimpanzee, it is most likely too early to see clinical symptoms in the infected pig-tailed macaques. The results thusfar indicate that HIV-1 infection of pig-tailed macaques may be similar to the infection seen in some humans: in the case of PT99 the infection is non-progressing whereas PT86 might represent a long-term survivor. Additional pig-tailed macaques have been infected with a preparation of HIV-1 produced in pig-tailed macaque PBMCs indicating reproducible infection of this species with a virus stock of HIV-1. To simulate the human situation where latent HIV-1 can be transiently stimulated with some vaccine injections, PT86, PT99 and other control animals were injected with tetanus toxoid without adjuvant. PBMCs were collected at the times points published for the human studies. The samples are currently being evaluated for virus isolation. HIV-1 DNA vaccine (CMV-DNA) produced persistent and boostable Gag and Env humoral repsonses in pig-tailed monkeys. The pig-tailed macaque model will be useful in evaluating protection by HIV-1 plasmid DNA vaccine against homologous challenge virus infection (HIV-1/LAI).