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

Devin Sok; Marit J. van Gils; Matthias Pauthner; Jean-Philippe Julien; Karen L. Saye-Francisco; Jessica Hsueh; Bryan Briney; Jeong Hyun Lee; Khoa M. Le; Peter S. Lee; Yuanzi Hua; Michael S. Seaman; John P. Moore; Andrew B. Ward; Ian A. Wilson; Rogier W. Sanders; Dennis R. Burton

doi:https://doi.org/10.1073/pnas.1415789111

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

Devin Sok, Marit J. van Gils, Matthias Pauthner, Jean-Philippe Julien, Karen L. Saye-Francisco, Jessica Hsueh, Bryan Briney, Jeong Hyun Lee, Khoa M. Le, Peter S. Lee, Yuanzi Hua, Michael S. Seaman, John P. Moore, Andrew B. Ward, Ian A. Wilson, Rogier W. Sanders, Dennis R. Burton

Research output: Contribution to journal › Article › Academic › peer-review

269 Citations (Scopus)

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

Original language	English
Pages (from-to)	17624-17629
Journal	PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume	111
Issue number	49
DOIs	https://doi.org/10.1073/pnas.1415789111
Publication status	Published - 2014

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https://doi.org/10.1073/pnas.1415789111

Cite this

Sok, D., van Gils, M. J., Pauthner, M., Julien, J.-P., Saye-Francisco, K. L., Hsueh, J., Briney, B., Lee, J. H., Le, K. M., Lee, P. S., Hua, Y., Seaman, M. S., Moore, J. P., Ward, A. B., Wilson, I. A., Sanders, R. W., & Burton, D. R. (2014). Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111(49), 17624-17629. https://doi.org/10.1073/pnas.1415789111

@article{dfc2983f2c6b4bf1ad76298aae91011a,

title = "Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex",

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",

author = "Devin Sok and {van Gils}, {Marit J.} and Matthias Pauthner and Jean-Philippe Julien and Saye-Francisco, {Karen L.} and Jessica Hsueh and Bryan Briney and Lee, {Jeong Hyun} and Le, {Khoa M.} and Lee, {Peter S.} and Yuanzi Hua and Seaman, {Michael S.} and Moore, {John P.} and Ward, {Andrew B.} and Wilson, {Ian A.} and Sanders, {Rogier W.} and Burton, {Dennis R.}",

year = "2014",

doi = "https://doi.org/10.1073/pnas.1415789111",

language = "English",

volume = "111",

pages = "17624--17629",

journal = "PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA",

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Sok, D, van Gils, MJ, Pauthner, M, Julien, J-P, Saye-Francisco, KL, Hsueh, J, Briney, B, Lee, JH, Le, KM, Lee, PS, Hua, Y, Seaman, MS, Moore, JP, Ward, AB, Wilson, IA, Sanders, RW & Burton, DR 2014, 'Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex', PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 111, no. 49, pp. 17624-17629. https://doi.org/10.1073/pnas.1415789111

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AU - Sok, Devin

AU - van Gils, Marit J.

AU - Pauthner, Matthias

AU - Julien, Jean-Philippe

AU - Saye-Francisco, Karen L.

AU - Hsueh, Jessica

AU - Briney, Bryan

AU - Lee, Jeong Hyun

AU - Le, Khoa M.

AU - Lee, Peter S.

AU - Hua, Yuanzi

AU - Seaman, Michael S.

AU - Moore, John P.

AU - Ward, Andrew B.

AU - Wilson, Ian A.

AU - Sanders, Rogier W.

AU - Burton, Dennis R.

PY - 2014

Y1 - 2014

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AB - 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

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DO - https://doi.org/10.1073/pnas.1415789111

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