期刊
IMMUNITY
卷 44, 期 5, 页码 1215-1226出版社
CELL PRESS
DOI: 10.1016/j.immuni.2016.04.016
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类别
资金
- IAVI
- Bill & Melinda Gates Foundation
- Ministry of Foreign Affairs of Denmark
- Irish Aid
- Ministry of Finance of Japan
- World Bank
- Ministry of Foreign Affairs of the Netherlands
- Norwegian Agency for Development Cooperation
- United Kingdom Department for International Development
- United States Agency for International Development (USAID)
- National Institute of Allergy And Infectious Diseases [U19AI090970, UM1AI100663]
- [U01GM110749]
- [AI100665]
- [K99AI120851]
- [R01 AI084817]
The high-mannose patch on HIV Env is a preferred target for broadly neutralizing antibodies (bnAbs), but to date, no vaccination regimen has elicited bnAbs against this region. Here, we present the development of a bnAb lineage targeting the high-mannose patch in an HIV-1 subtype-C-infected donor from sub-Saharan Africa. The Abs first acquired autologous neutralization, then gradually matured to achieve breadth. One Ab neutralized >47% of HIV-1 strains with only similar to 11% somatic hypermutation and no insertions or deletions. By sequencing autologous env, we determined key residues that triggered the lineage and participated in Ab-Env coevolution. Next-generation sequencing of the Ab repertoire showed an early expansive diversification of the lineage followed by independent maturation of individual limbs, several of them developing notable breadth and potency. Overall, the findings are encouraging from a vaccine standpoint and suggest immunization strategies mimicking the evolution of the entire high-mannose patch and promoting maturation of multiple diverse Ab pathways.
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