期刊
NATURE MEDICINE
卷 18, 期 11, 页码 1688-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.2985
关键词
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资金
- CAPRISA
- Centre for HIV/AIDS Vaccine Immunology
- South African HIV/AIDS Research and Innovation Platform of the South African Department of Science and Technology
- US National Institutes of Health [AI088610]
- US Department of Health and Human Services
- US National Institute of Allergy and Infectious Diseases, US National Institutes of Health, US Department of Health and Human Services [U19 AI51794]
- Bill & Melinda Gates Foundation
- Vaccine Immune Monitoring Consortium of the Collaboration for AIDS Vaccine Discovery [1032144]
- Columbia University-Southern African Fogarty AIDS International Training and Research Program through the Fogarty International Center, National Institutes of Health [5 D43 TW000231]
- Wellcome Trust [089933/Z/09/Z]
- Wellcome Trust [089933/Z/09/Z] Funding Source: Wellcome Trust
Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful(1-3), a minority of individuals naturally develop these antibodies after many years of infection(4-7). How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1-infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes.
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