期刊
IMMUNITY
卷 38, 期 1, 页码 176-186出版社
CELL PRESS
DOI: 10.1016/j.immuni.2012.11.011
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类别
资金
- Bill & Melinda Gates Foundation
- NIH/NIAID [AI067854, AI100645]
- Department of Veterans Affairs [Y1-AI-2642-12]
- U.S. Army Medical Research and Material Command (USAMRMC) [Y1-AI-2642-12]
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]
- U.S. Department of Defense (DOD) [W81XWH-07-2-0067]
- NIH
- NIH grants [S10RR019145, UC6 AI058607, AI64518, P30 AI051445]
The RV144 HIV-1 trial of the canary pox vector (ALVAC-HIV) plus the gp120 AIDSVAX B/E vaccine demonstrated an estimated efficacy of 31%, which correlated directly with antibodies to HIV-1 envelope variable regions 1 and 2 (V1-V2). Genetic analysis of trial viruses revealed increased vaccine efficacy against viruses matching the vaccine strain at V2 residue 169. Here, we isolated four V2 monoclonal antibodies from RV144 vaccinees that recognize residue 169, neutralize laboratory-adapted HIV-1, and mediate killing of field-isolate HIV-1-infected CD4(+) T cells. Crystal structures of two of the V2 antibodies demonstrated that residue 169 can exist within divergent helical and loop conformations, which contrasted dramatically with the 13 strand conformation previously observed with a broadly neutralizing antibody PG9. Thus, RV144 vaccine-induced immune pressure appears to target a region that may be both sequence variable and structurally polymorphic. Variation may signal sites of HIV-1 envelope vulnerability, providing vaccine designers with new options.
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