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¹ AIDS Vaccine Research Laboratory, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53715
² Department of Medical Biochemistry and Immunology, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, Wales, UK
³ Department of Biostatistics, Section on Statistical Genetics, University of Alabama at Birmingham, Birmingham, AL 35294
⁴ International AIDS Vaccine Initiative, New York, NY 10038
⁵ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037
⁶ Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706

CORRESPONDENCE Matthew Reynolds: mrreynol{at}wisc.edu

An effective AIDS vaccine will need to protect against globally diverse isolates of HIV. To address this issue in macaques, we administered a live-attenuated simian immunodeficiency virus (SIV) vaccine and challenged with a highly pathogenic heterologous isolate. Vaccinees reduced viral replication by 2 logs between weeks 2–32 (P 0.049) postchallenge. Remarkably, vaccinees expressing MHC-I (MHC class I) alleles previously associated with viral control completely suppressed acute phase replication of the challenge virus, implicating CD8⁺ T cells in this control. Furthermore, transient depletion of peripheral CD8⁺ lymphocytes in four vaccinees during the chronic phase resulted in an increase in virus replication. In two of these animals, the recrudescent virus population contained only the vaccine strain and not the challenge virus. Alarmingly, however, we found evidence of recombinant viruses emerging in some of the vaccinated animals. This finding argues strongly against an attenuated virus vaccine as a solution to the AIDS epidemic. On a more positive note, our results suggest that MHC-I–restricted CD8⁺ T cells contribute to the protection induced by the live-attenuated SIV vaccine and demonstrate that vaccine-induced CD8⁺ T cell responses can control replication of heterologous challenge viruses.

© 2008 Reynolds et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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