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,,¶,¶
* Department of Pathology and
Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104;
Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329;
Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104; and
¶ Merck Vaccines and Infectious Diseases, Merck and Co., West Point, PA 19486
Our limited understanding of the interaction between primate lentiviruses and the host immune system complicates the design of an effective HIV/AIDS vaccine. To identify immunological correlates of protection from SIV disease progression, we immunized two groups of five rhesus macaques (RMs) with either modified vaccinia Ankara (MVA) or MVA
udg vectors that expressed SIVmac239 Gag and Tat. Both vectors raised a SIV-specific CD8+ T cell response, with a magnitude that was greater in mucosal tissues than in peripheral blood. After challenge with SIVmac239, all vaccinated RMs showed mucosal and systemic CD8+ T cell recall responses that appeared faster and were of greater magnitude than those in five unvaccinated control animals. All vaccinated RMs showed a 
1-log lower peak and early set-point SIV viral load than the unvaccinated animals, and then, by 8 wk postchallenge, exhibited levels of viremia similar to the controls. We observed a significant direct correlation between the magnitude of postchallenge SIV-specific CD8+ T cell responses and SIV viral load. However, vaccinated RMs showed no protection from either systemic or mucosal CD4+ T cell depletion and no improved survival. The observation that vaccine-induced, SIV-specific CD8+ T cells that partially control SIVmac239 virus replication fail to protect from immunological or clinical progression of SIV infection underscores both the complexity of AIDS pathogenesis and the challenges of properly assessing the efficacy of candidate AIDS vaccines.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This research was supported by Integrated Preclinical and Clinical AIDS Vaccine Development Grant U19-AI 061728 (to J.D.A., S.I.S., D.A.G., M.B.F., and G.S.) and in part by the Virology and Drug Discovery Core of the Emory Center for AIDS Research (Grant P30 AI050409) and Grant P51-RR00165 to the Yerkes National Primate Research Center.
2 J.C.E. and R.M.D. contributed equally to the study.
3 Address correspondence and reprint requests to Dr. Guido Silvestri, 705 Stellar-Chance Laboratories, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, PA. E-mail address: gsilvert{at}mail.med.upenn.edu
4 Abbreviations used in this paper: Ad, adenovirus; MVA, modified vaccinia Ankara; RM, rhesus macaque; BAL, bronchoalveolar lavage; TCID50, 50% tissue culture-infective dose; LN, lymph note; RB, rectal biopsy.
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