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 post-infection. 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 HIV-1 gag and env proteins have persisted in PT86 where in PT99 only antibodies to the env proteins were seen and have persisted. Higher Env titers were seen in PT 86 and PT 99 at 3 years post-infection than at 6 years post-infection. Although the CD4+/CD8+ ratio gradually declined in PT 86 and was maintained at a lower level, 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. Another pig-tailed macaque was recently infected a lower dose of HIV-1 and developed antibodies to Gag and Env. Studies are currently underway to determine the viral load in the infected animals to further evaluate HIV-1 infection in pig-tailed macaques as a model for human long-term non-progressors. To analyze activation of latent HIV-1, 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. Virus induction was not seen. However, in another to evaluate tetanus toxoid potency, it was also found that the antibody response to tetanus toxoid without adjuvant was less than that seen in the case of toxoid with adjuvant. The animals will be injected with the potent tetanus toxoid to further analyze HIV-1 activation in infected pig-tailed monkeys. HIV-1 DNA vaccine (CMV-DNA) produced persistent and boostable Gag and Env humoral repsonses in pig-tailed monkeys. The DNA immunized pig-tailed macaques were challenged with homologous virus (HIV-1/LAI). Studies are underway to evaluate efficacy of the DNA vaccine in HIV-1 infected pig-tailed macaque model.