HIV-1 VACCINES. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen.

TitleHIV-1 VACCINES. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen.
Publication TypeJournal Article
Year of Publication2015
AuthorsJardine JG, Ota T, Sok D, Pauthner M, Kulp DW, Kalyuzhniy O, Skog PD, Thinnes TC, Bhullar D, Briney B, Menis S, Jones M, Kubitz M, Spencer S, Adachi Y, Burton DR, Schief WR, Nemazee D
JournalScience
Volume349
Issue6244
Pagination156-61
Date Published07/10/2015
ISSN1095-9203
Abstract

A major goal of HIV-1 vaccine research is the design of immunogens capable of inducing broadly neutralizing antibodies (bnAbs) that bind to the viral envelope glycoprotein (Env). Poor binding of Env to unmutated precursors of bnAbs, including those of the VRC01 class, appears to be a major problem for bnAb induction. We engineered an immunogen that binds to VRC01-class bnAb precursors and immunized knock-in mice expressing germline-reverted VRC01 heavy chains. Induced antibodies showed characteristics of VRC01-class bnAbs, including a short CDRL3 (light-chain complementarity-determining region 3) and mutations that favored binding to near-native HIV-1 gp120 constructs. In contrast, native-like immunogens failed to activate VRC01-class precursors. The results suggest that rational epitope design can prime rare B cell precursors for affinity maturation to desired targets.

DOI10.1126/science.aac5894
Alternate JournalScience
PubMed ID26089355
Grant List1UM1AI100663 / AI / NIAID NIH HHS / United States
P01AI081625 / AI / NIAID NIH HHS / United States
R01-AI073148 / AI / NIAID NIH HHS / United States
CHAVI-ID: 
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