Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex.

TitleRecombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex.
Publication TypeJournal Article
Year of Publication2014
AuthorsSok D, van Gils MJ, Pauthner M, Julien J-P, Saye-Francisco KL, Hsueh J, Briney B, Lee J H, Le KM, Lee PS, Hua Y, Seaman MS, Moore JP, Ward AB, Wilson IA, Sanders RW, Burton DR
JournalProc Natl Acad Sci U S A
Volume111
Issue49
Pagination17624-9
Date Published12/09/2014
ISSN1091-6490
Abstract

Broadly neutralizing antibodies (bnAbs) targeting the trimer apex of HIV envelope are favored candidates for vaccine design and immunotherapy because of their great neutralization breadth and potency. However, methods of isolating bnAbs against this site have been limited by the quaternary nature of the epitope region. Here we report the use of a recombinant HIV envelope trimer, BG505 SOSIP.664 gp140, as an affinity reagent to isolate quaternary-dependent bnAbs from the peripheral blood mononuclear cells of a chronically infected donor. The newly isolated bnAbs, named "PGDM1400-1412," show a wide range of neutralization breadth and potency. One of these variants, PGDM1400, is exceptionally broad and potent with cross-clade neutralization coverage of 83% at a median IC50 of 0.003 µg/mL. Overall, our results highlight the utility of BG505 SOSIP.664 gp140 as a tool for the isolation of quaternary-dependent antibodies and reveal a mosaic of antibody responses against the trimer apex within a clonal family.

DOI10.1073/pnas.1415789111
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID25422458
PubMed Central IDPMC4267403
Grant List5T32AI007606-10 / AI / NIAID NIH HHS / United States
P01 AI82362 / AI / NIAID NIH HHS / United States
R01 AI033292 / AI / NIAID NIH HHS / United States
R01 AI84817 / AI / NIAID NIH HHS / United States
R37 AI36082 / AI / NIAID NIH HHS / United States
UM1AI100663 / AI / NIAID NIH HHS / United States
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