The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization.

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TitleThe HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization.
Publication TypeJournal Article
Year of Publication2019
AuthorsLei, L, Yang, YR, Tran, K, Wang, Y, Chiang, C-I, Ozorowski, G, Xiao, Y, Ward, AB, Wyatt, RT, Li, Y
JournalCell Rep
Volume27
Issue2
Pagination586-598.e6
Date Published2019 Apr 09
ISSN2211-1247
Abstract

Despite recent progress in engineering native trimeric HIV-1 envelope glycoprotein (Env) mimics as vaccine candidates, Env trimers often induce vaccine-matched neutralizing antibody (NAb) responses. Understanding the specificities of autologous NAb responses and the underlying molecular mechanisms restricting the neutralization breadth is therefore informative to improve vaccine efficacy. Here, we delineate the response specificity by single B cell sorting and serum analysis of guinea pigs immunized with BG505 SOSIP.664 Env trimers. Our results reveal a prominent immune target containing both conserved and strain-specific residues in the C3/V4 region of Env in trimer-vaccinated animals. The defined NAb response shares a high degree of similarity with the early NAb response developed by a naturally infected infant from whom the HIV virus strain BG505 was isolated and later developed a broadly NAb response. Our study describes strain-specific responses and their possible evolution pathways, thereby highlighting the potential to broaden NAb responses by immunogen re-design.

DOI10.1016/j.celrep.2019.03.039
Alternate JournalCell Rep
PubMed ID30970260
Grant ListR01 AI102766 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States