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150 Retooling the Macaque Model as a Necessary Step to Evaluate the Relative Efficacy of Vaccines for HIV

Franchini, Genoveffa

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 61
doi: 10.1097/01.qai.0000397335.02858.d2

Animal Models and Retroviral Vaccines Section, VB, NCI, NIH Bethesda MD

Vaccination with ALVAC-HIV and gp120 protein demonstrated some degree of protection against HIV acquisition (31.2%), in the RV144 Trial. We have investigated how the dose of challenge exposure to SIVmac251 affects the evaluation of relative vaccine efficacy in macaques. We have chosen vaccine regimens that closely mimic the RV144 trial, since this is the only vaccine regiment that, so far, has given some degree of protection in humans. Vaccine regimens that included DNA/ALVAC-SIV/gp120 or ALVAC-SIV/ gp120 or gp120 alone have been re-evaluated using a single high dose or repeated lower doses of SIV mac 251. These vaccines induced CD4+, CD8+T-cell responses, and antibodies levels as observed in humans. Minimal protection was observed in macaques exposed to a single high virus dose. In contrast, exposure to the lower virus doses resulted in protection from acquisition in three of the twelve vaccinated macaques. None of the naive controls were protected. The nine vaccinated animals that became infected had significantly lower virus in plasma and at the mucosal site than control macaques and, strikingly, they were also protected from the systemic CD4+T-cells loss and experienced a significantly better reconstitution of CD4+T-cells at mucosal sites. Analysis of immune correlates was doable only in animals that became infected because of the small number of those that were protected from acquisition (3 of 12). Nevertheless, the immune responses that correlated inversely with short and/or long term control of virus level were mainly CD4+T-cell responses (ICC and Lymph proliferative responses for envelope) and ADCC. Our results suggest that a properly calibrated macaque model may become a useful tool to understand immune correlates of protection and promote a rapid progress in the development of more effective vaccines for HIV.

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