期刊
JOURNAL OF INFECTIOUS DISEASES
卷 214, 期 3, 页码 379-389出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiw093
关键词
HLA class I; HIV-1 vaccine; Phambili trial; Gag-specific CD8+T cells
资金
- NIH [RO1AI46995]
- Wellcome Trust [WT104748MA]
- NIAID [UM1AI068618, 5U01 AI068614, 5U01 AI068618, 5U01 AI068635, 5U01 AI069453, 5U01 AI069519, 5U01 AI069469]
- National Institute of Health Research (NIHR)
- South African Research Chairs Initiative
- Victor Daitz Foundation
- Howard Hughes Medical Institute
- MRC [G0501777] Funding Source: UKRI
- Medical Research Council [G0501777] Funding Source: researchfish
- National Institute for Health Research [CL-2011-13-005] Funding Source: researchfish
Background. HLA strongly influences human immunodeficiency virus type 1 (HIV-1) disease progression. A major contributory mechanism is via the particular HLA-presented HIV-1 epitopes that are recognized by CD8(+) T-cells. Different populations vary considerably in the HLA alleles expressed. We investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag/Pol/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B(star)58:02 is highly prevalent. Methods. Viral loads, CD4(+) T-cell counts, and enzyme-linked immunospot assay-determined anti-HIV-1 CD8(+) T-cell responses for a subset of infected antiretroviral-naive Phambili participants, selected according to sample availability, were analyzed. Results. Among those expressing disease-susceptible HLA-B(star)58: 02, vaccinees had a lower chronic viral set point than placebo recipients (median, 7240 vs 122 500 copies/mL; P =.01), a 0.76 log(10) lower longitudinal viremia level (P =.01), and slower progression to a CD4(+) T-cell count of <350 cells/mm(3) (P = .02). These differences were accompanied by a higher Gag-specific breadth (4.5 vs 1 responses; P = .04) and magnitude (2300 vs 70 spot-forming cells/10(6) peripheral blood mononuclear cells; P = .06) in vaccinees versus placebo recipients. Conclusions. In addition to the known enhancement of HIV-1 acquisition resulting from the MRKAd5 HIV-1 vaccine, these findings in a nonrandomized subset of enrollees show an HLA-specific vaccine effect on the time to CD4+ T-cell count decline and viremia level after infection and the potential for vaccines to differentially alter disease outcome according to population HLA composition.
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