|Title||Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex.|
|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Sok 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|
|Journal||Proc Natl Acad Sci U S A|
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.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|
|PubMed Central ID||PMC4267403|
|Grant List||5T32AI007606-10 / 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
Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex.