HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen.

TitleHIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen.
Publication TypeJournal Article
Year of Publication2016
AuthorsJardine JG, Kulp DW, Havenar-Daughton C, Sarkar A, Briney B, Sok D, Sesterhenn F, Ereño-Orbea J, Kalyuzhniy O, Deresa I, Hu X, Spencer S, Jones M, Georgeson E, Adachi Y, Kubitz M, DeCamp AC, Julien J-P, Wilson IA, Burton DR, Crotty S, Schief WR
JournalScience
Volume351
Issue6280
Pagination1458-63
Date Published03/25/2016
ISSN1095-9203
Abstract

Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naïve B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. Using deep mutational scanning and multitarget optimization, we developed a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naïve B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen as a candidate human vaccine prime. These methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.

DOI10.1126/science.aad9195
Alternate JournalScience
PubMed ID27013733
Grant ListP01 AI094419 / AI / NIAID NIH HHS / United States
P01 AI110657 / AI / NIAID NIH HHS / United States
P41GM103393 / GM / NIGMS NIH HHS / United States
R01 AI084817 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
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