期刊
IMMUNITY
卷 50, 期 3, 页码 677-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2019.02.008
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资金
- Henry M. Jack-son Foundation for the Advancement of Military Medicine, Inc. [W81XWH-07-2-0067, W81XWH-11-2-0174, W81XWH-18-2-0040]
- U.S.Department of Defense (DOD), United States [W81XWH-07-2-0067, W81XWH-11-2-0174, W81XWH-18-2-0040]
- Leidos Biomedical Research Inc. [15X219]
- DTRA [HDTRA1-12C-0105]
- Frederick National Laboratory for Cancer Research [HHSN261200800001E]
- Intramural Research Program of the Vaccine Research Center, NIAID, National Institutes of Health, United States
- United States Department of Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
- [R01 AI131722]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [ZIAAI005024, ZIAAI005143, ZIAAI005095, ZICAI005111, ZICAI005133, ZIAAI005033, ZICAI005114] Funding Source: NIH RePORTER
Lineage-based vaccine design is an attractive approach for eliciting broadly neutralizing antibodies (bNAbs) against HIV-1. However, most bNAb lineages studied to date have features indicative of unusual recombination and/or development. From an individual in the prospective RV217 cohort, we identified three lineages of bNAbs targeting the membrane-proximal external region (MPER) of the HIV-1 envelope. Antibodies RV217-VRC42.01, -VRC43.01, and -VRC46.01 used distinct modes of recognition and neutralized 96%, 62%, and 30%, respectively, of a 208-strain virus panel. All three lineages had modest levels of somatic hypermutation and normal antibody-loop lengths and were initiated by the founder virus MPER. The broadest lineage, VRC42, was similar to the known bNAb 4E10. A multimeric immunogen based on the founder MPER activated B cells bearing the unmutated common ancestor of VRC42, with modest maturation of early VRC42 intermediates imparting neutralization breadth. These features suggest that VRC42 may be a promising template for lineage-based vaccine design.
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