Priming HIV-1 broadly neutralizing antibody precursors in human Ig loci transgenic mice.

TitlePriming HIV-1 broadly neutralizing antibody precursors in human Ig loci transgenic mice.
Publication TypeJournal Article
Year of Publication2016
AuthorsSok D, Briney B, Jardine JG, Kulp DW, Menis S, Pauthner M, Wood A, Lee E-C, Le KM, Jones M, Ramos A, Kalyuzhniy O, Adachi Y, Kubitz M, Macpherson S, Bradley A, Friedrich GA, Schief WR, Burton DR
JournalScience
Volume353
Issue6307
Pagination1557-1560
Date Published09/30/2016
ISSN1095-9203
Abstract

A major obstacle to a broadly neutralizing antibody (bnAb)-based HIV vaccine is the activation of appropriate B cell precursors. Germline-targeting immunogens must be capable of priming rare bnAb precursors in the physiological setting. We tested the ability of the VRC01-class bnAb germline-targeting immunogen eOD-GT8 60mer (60-subunit self-assembling nanoparticle) to activate appropriate precursors in mice transgenic for human immunoglobulin (Ig) loci. Despite an average frequency of, at most, about one VRC01-class precursor per mouse, we found that at least 29% of singly immunized mice produced a VRC01-class memory response, suggesting that priming generally succeeded when at least one precursor was present. The results demonstrate the feasibility of using germline targeting to prime specific and exceedingly rare bnAb-precursor B cells within a humanlike repertoire.

DOI10.1126/science.aah3945
Alternate JournalScience
PubMed ID27608668
Grant ListP01 AI094419 / AI / NIAID NIH HHS / United States
UM1 AI100663 / AI / NIAID NIH HHS / United States
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