Therapeutic use of a recombinant attenuated pox virus vaccine in SIV-infected macaques.
Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. MoOrA104)
Franchini G, Hel Z, Poudyal M, Tsai W-P, Giuliani L, Woodward R, Chougnet C, Shearer G, Altman J, Watkins D, Bischofberger N, Abimiku A, Markham P, Tartaglia J Z.~Hel, National Cancer Institute, 41 Library Drive, Room D804, Bethesda, Maryland 20892, United States, Tel.: +301-496-23-86, Fax: +301-402-00-55, E-mail: veffa@helix.nih.gov
The highly attenuated NYVAC-SIV-gag-pol-env (gpe)-based vaccine prevents infection and/or the development of AIDS in the SIV251 rhesus macaque model. We modeled this vaccine as a potential therapeutic agent in seroconverter macaques treated with HAART. The NYVAC-SIV-gpe vaccine induced significant levels of SIV p27 Gag- and Env-specific CD4+ helper responses as well as a significant expansion of the number of SIV-Gag-specific CD3+ CD8+ T-cells, with effector function only in animals in which viremia was suppressed by HAART. Following the suspension of HAART, viral rebound occurred in animals mock-vaccinated and NYVAC-SIV-gpe-vaccinated. However, the plasma virus load was significantly lower in the NYVAC-SIV-vaccinated animals than in the mock-vaccinated group. Viremia suppression correlated with the resurgence, or induction by vaccination, of SIV p27 Gag CD4+ T-helper responses before therapy suspension, and these responses were further boosted by the initial viral rebound. Similarly, the level of Gag-specific Mamu-A*01-p11C, C M-tetramer CD8+ T-cells in PBMC was boosted by the initial viral rebound. All together, these data demonstrate that early intervention with HAART per se results in viremia control and that immune intervention is effective in the context of HAART. Whether HAART and NYVAC-SIV vaccination synergize awaits studies with a larger number of macaques and/or trials in HIV-I-infected individuals.
Keywords: AEGIS, SIV, SAIDS Vaccines, Macaca, Vaccines, Synthetic, Macaca mulatta, Viremia, Vaccinia virus, Vaccination, Chordopoxvirinae, Avipoxvirus, Animal, immunology 000709
MoOrA104
