| Literature DB >> 26725118 |
Todd Bradley1, Daniela Fera2, Jinal Bhiman3, Leila Eslamizar4, Xiaozhi Lu5, Kara Anasti5, Ruijung Zhang5, Laura L Sutherland5, Richard M Scearce5, Cindy M Bowman5, Christina Stolarchuk5, Krissey E Lloyd5, Robert Parks5, Amanda Eaton5, Andrew Foulger5, Xiaoyan Nie5, Salim S Abdool Karim6, Susan Barnett7, Garnett Kelsoe5, Thomas B Kepler8, S Munir Alam5, David C Montefiori5, M Anthony Moody5, Hua-Xin Liao5, Lynn Morris9, Sampa Santra4, Stephen C Harrison10, Barton F Haynes11.
Abstract
Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization.Entities:
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Year: 2015 PMID： 26725118 PMCID： PMC4706810 DOI： 10.1016/j.celrep.2015.12.017
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423