[control of HIV by vaccine-elicited HIV-specific T cell responses may be difficult]
>>Published online before print March 7, 2005
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0408773102
OPEN ACCESS ARTICLE
pnas.org
Immunology
Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection
( acute infection | correlate of protection | multiparameter flow cytometry )
Michael R. Betts a, Barbara Exley b, David A. Price c, Anju Bansal d, Zenaido Tres Camacho e, Vanessa Teaberry b, Sadie M. West a, David R. Ambrozak a, Georgia Tomaras b, Mario Roederer f, J. Michael Kilby d, Jim Tartaglia g, Robert Belshe h, Feng Gao e, Daniel C. Douek c, Kent J. Weinhold a, Richard A. Koup a, Paul Goepfert d,i, and Guido Ferrari b,i,j
aLaboratory of Immunology, cHuman Immunology Section, and fImmunoTechnology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892; bDepartment of Surgery, Duke University Medical Center, SORF Building, La Salle Street Extension, Durham, NC 27710; dUniversity of Alabama at Birmingham, 845 19th Street South, BBRB 20, Birmingham, AL 35294; eHuman Vaccine Institute, Duke University Medical Center, 112 Research Park III, Research Drive, Durham, NC 27710; gR&D Aventis Pasteur, 1755 Steeles Avenue West, Toronto, Ontario, Canada M2R 3T4; and hDepartment of Medicine, Saint Louis University Hospital FDT-8, 3635 Vista Avenue, St. Louis, MO 63119
Edited by Robert C. Gallo, Institute of Human Virology, Baltimore, MD, and approved January 25, 2005 (received for review November 24, 2004)
Worldwide HIV-1 vaccine efforts are guided by the principle that HIV-specific T cell responses may provide protection from infection or delay overt disease. However, no clear correlates of T cell-mediated immune protection have been identified. Here, we examine in a HLA-B27+ HIV seronegative vaccinee persistent HIV-specific vaccine-induced anti-Gag CD4+ and CD8+ T cell responses. Although these responses exhibited those characteristics (multifunctionality, appropriate memory phenotype, and targeting of epitopes associated with long-term nonprogression) predicted to correlate with protection from infection, the subject became HIV infected. After HIV infection, the vaccine-induced CD8+ T cells expanded, but both CD4+ and CD8+ T cell responses acquired the functional and phenotypic patterns characteristic of chronic HIV infection. The virus quickly escaped the vaccine-induced T cell response, and the subject progressed more rapidly than expected for someone expressing the HLA-B27 allele. These data suggest that control of HIV by vaccine-elicited HIV-specific T cell responses may be difficult, even when the T cell response has those characteristics predicted to provide optimal protection.<<
Helps explain, say, VaxGen's failure here?
Cheers, Tuck |
