17th International AIDS Conference Mexico City, Mexico - August 13 - 18, 2008

HUMORAL IMMUNE RESPONSES HAVE LITTLE EFFECT ON CONTROLLING VIREMIA DURING SIVagm INFECTION OF AFRICAN GREEN MONKEYS

Int Conf AIDS. 2008 Aug 13-18;17 Abstract No. MoAa0101

T. Gaufin¹, M. Pattison¹, C. Stoulig¹, R. Gautam¹, M. Barnes¹, C. Monjure¹, M. Marx¹, D. Montefiori², C. Apetrei¹, I. Pandrea¹
1Tulane National Primate Research Center, Covington, United States, ²Duke University, Durham, United States

BACKGROUND: SIV-infected African nonhuman primates (NHPs) do not progress to AIDS despite active and persistent viral replication of the same magnitude or higher than in pathogenic infections. It has been suggested that higher viral loads (VLs) in chronic, natural SIV infections are due to lower anti-SIV antibody titers in SIV-infected African NHPs, which implies a role for antibodies in controlling VLs. We investigated the impact of antibody responses on SIVagm replication in African green monkeys (AGMs).

METHODS: Ten AGMs were inoculated with 300 TCID₅₀ of SIVagm.sab. Four AGMs received 50 mg/kg of Rituxan (anti-CD20 antibody, gift from Genentech) every 21 days, starting from day -7 post-infection. Remaining AGMs received only SIVagm.sab. VLs in plasma and tissues were determined by real-time PCR and in situ hybridization (ISH). Dynamics of the major lymphocyte subsets were measured in peripheral blood, lymph nodes (LNs) and intestine by flow-cytometry. T-cell Immune activation, proliferation and apoptosis were investigated by flow-cytometry and immunohistochemistry. Differences in the emergence of anti-SIV antibodies were compared by serology.

RESULTS: All Rituxan-treated AGMs successfully depleted CD20 cells in peripheral blood, LNs and intestine, as illustrated by the dynamics of CD20+ and CD79a+ cells. There was no significant difference in VLs between CD20-depleted AGMs and control monkeys: during acute infection peak VLs ranged 10⁷-10⁸ copies/ml; during chronic infection, set-point values ranged from 10⁴ to 10⁵ SIV RNA copies/ml. Levels of acute CD4 T-cell depletion in the intestine were similar in treated and non-treated animals. The production of anti-SIV antibodies and neutralizing antibodies was ablated in the CD20-depleted AGMs compared to the controls. CD20 depletion resulted in effacing the histological structure of the germinal centers in the LNs and Peyer‘s patches.

CONCLUSIONS: Our study shows that humoral immune responses play no significant role in SIV viral replication control during acute and chronic SIVagm infection in the natural host.

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2008-08-13
MoAa0101

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