Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection.
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.
Betts
Michael R
MR
Laboratory of Immunology, Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, USA.
Exley
Barbara
B
Price
David A
DA
Bansal
Anju
A
Camacho
Zenaido Tres
ZT
Teaberry
Vanessa
V
West
Sadie M
SM
Ambrozak
David R
DR
Tomaras
Georgia
G
Roederer
Mario
M
Kilby
J Michael
JM
Tartaglia
Jim
J
Belshe
Robert
R
Gao
Feng
F
Douek
Daniel C
DC
Weinhold
Kent J
KJ
Koup
Richard A
RA
Goepfert
Paul
P
Ferrari
Guido
G
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics; D015683:Gene Products, gag / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control* / Q000635:transmission; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000378:metabolism; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D013601:T-Lymphocytes / Q000276:immunology*
D016915:AIDS Vaccines; D004279:DNA, Viral; D015683:Gene Products, gag; D015796:HLA-B27 Antigen