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The Journal of Immunology, 2003, 171: 1094-1101.
Copyright © 2003 by The American Association of Immunologists

HIV-1 Vaccination Administered Intramuscularly Can Induce Both Systemic and Mucosal T Cell Immunity in HIV-1-Uninfected Individuals

Luwy Musey*, Yan Ding{dagger}, Marnie Elizaga*,{dagger}, Richard Ha{dagger}, Connie Celum* and M. Juliana McElrath2,*,{dagger}

* Department of Medicine, University of Washington, Seattle, WA 98195; and {dagger} Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109

A vaccine regimen that can rapidly control HIV-1 replication at the site of exposure following sexual contact is likely to be the most effective in preventing HIV-1 infection. As part of a larger, phase II clinical trial, we evaluated the ability of a recombinant canarypox HIV-1 vaccine to induce CTL that can be detected in both the systemic and mucosal compartments following i.m. immunization in 12 low- and high-risk HIV-1 seronegative volunteers. In the 7 volunteers receiving four immunizations with live recombinant canarypox ALVAC-HIV vaccine with or without rgp120/SF-2, HIV-1-specific CTL were detected in the blood of 5 (71%) and in the rectum of 4 (57%). CTL responses were observed in both risk strata. In contrast, 5 volunteers receiving placebo had undetectable responses in both compartments. Vaccine-induced, HIV-1-specific effector activities included IFN-{gamma} secretion and class I MHC-restricted CD8+ CTL. Rectal and systemic CD8+ CTL clones established in 1 vaccine recipient revealed similar Env-specific responses and MHC restriction. These findings indicate that parenteral vaccination can induce HIV-1-specific CTL that localize to sites of HIV-1 acquisition, where their presence may be critical in the control of initial viral replication and eventual dissemination. Determination of the optimal strategy to induce mucosal T cells requires future clinical studies.




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