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SIV-specific CD8+ T-cells mediated protection from uncontrolled viral replication after vaginal challenge in live-attenuated immunised rhesus macaques

Abstract number: O522

Genescà M., Stone M., Lu D., Bost K.M., Li J., Rourke T.L., McChesney M.B., Miller C.J.

Objectives: Live-attenuated lentivirus immunisation protects rhesus monkeys from uncontrolled viral replication after vaginal challenge with pathogenic SIVmac239. Local polyfunctional Gag-specific CD4+ and CD8+T cell responses are present in the genital tract of SHIV89.6-immunised rhesus macaques at the time of SIV challenge. To further assess the role of CD8+ lymphocytes in vaccine-induced protection, a group of SHIV-vaccinated monkeys was depleted of CD8+ lymphocytes on the day of challenge with SIVmac239.

Methods: SHIV89.6-immunised (n = 12) and non-immunised (n = 9) animals where necropsied at 14 days post-challenge (PC). Anti-CD8 (cM T807; 50mg/kg) was administered to an additional group of immunised monkeys (n = 6) on the day of the intravaginal challenge with SIVmac239. Lymphocytes from freshly digested cervicovaginal tissues, lymph nodes and peripheral blood where analysed by polychromatic flow cytometry for Gag specific responses (intracellular cytokines, degranulation and cell death/survival signals).

Results: Viral RNA (vRNA) levels were high in all tissues of non-immunised animals (GI tract [Gt] systemic lymph nodes > genital tract). In immunised animals, virus replication was controlled in all tissues and SIV dissemination beyond the genital lymph nodes was limited. Only 2 immunised animals had moderate levels of vRNA in the GI tract and systemic tissues, with a similar distribution to the control animals. Strikingly, CD8+ lymphocyte depletion eliminated the beneficial effect of the SHIV immunisation, and by 7 days PC, this group had the highest plasma vRNA levels of all groups. Interestingly, the distribution of viral replication was different, and the highest levels of vRNA were found in the genital tract. Moreover, the only Mamu-A01*monkey in this group, which was the only animal that partially controlled the virus in the different tissues, was the only monkey with detectable specific CD8+T cell response in the genital lymph nodes.

Conclusion: In summary, the establishment of a memory SIV-specific polyfunctional T cell response in the genital tract induced by live-attenuated immunisation may account for protection from intravaginal SIV challenge. Further, depletion of CD8+T cells eliminates the live-attenuated lentivirus mediated protection.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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