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Absence of Immunodominant Anti-Gag p17 (SL9) Responses among Gag CTL-Positive, HIV-Uninfected Vaccine Recipients Expressing the HLA-A*0201 Allele¹

Guido Ferrari^2,*, Wesley Neal^*, Janet Ottinger^*, Anizsa M. Jones^*, Bradley H. Edwards, Paul Goepfert, Michael R. Betts, Richard A. Koup, Susan Buchbinder^¶, M. Juliana McElrath^||, Jim Tartaglia^# and Kent J. Weinhold^*,¶

Departments of ^* Surgery and Immunology, Duke University Medical Center, Durham, NC 27710; Department of Medicine, Division of Infectious Diseases, University of Alabama, Birmingham, AL 35294; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD 20892; ^¶ San Francisco Department of Public Health, San Francisco, CA 94102; ^|| Fred Hutchinson Cancer Research Center/University of Washington, Seattle, WA 981024; and ^# Aventis Pasteur, Toronto, Ontario, Canada

According to a number of previous reports, control of HIV replication in humans appears to be linked to the presence of anti-HIV-1 Gag-specific CD8 responses. During the chronic phase of HIV-1 infection, up to 75% of the HIV-infected individuals who express the histocompatibility leukocyte Ag (HLA)-A*0201 recognize the Gag p17 SLYNTVATL (aa residues 77–85) epitope (SL9). However, the role of the anti-SL9 CD8 CTL in controlling HIV-1 infection remains controversial. In this study we determined whether the pattern of SL9 immunodominance in uninfected, HLA-A*0201 HIV vaccine recipients is similar to that seen in chronically HIV-infected subjects. The presence of anti-SL9 responses was determined using a panel of highly sensitive cellular immunoassays, including peptide:MHC tetramer binding, IFN- ELISPOT, and cytokine flow cytometry. Thirteen HLA-A*0201 vaccinees with documented anti-Gag CD8 CTL reactivities were tested, and none had a detectable anti-SL9 response. These findings strongly suggest that the pattern of SL9 epitope immunodominance previously reported among chronically infected, HLA-A*0201-positive patients is not recapitulated in noninfected recipients of Gag-containing canarypox-based candidate vaccines and may be influenced by the relative immunogenicity of these constructs.

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