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Improving the immunogenicity of native-like HIV-1 envelope trimers by hyperstabilization

Improving the immunogenicity of native-like HIV-1 envelope trimers by hyperstabilization
Improving the immunogenicity of native-like HIV-1 envelope trimers by hyperstabilization

The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation. The resulting next-generation SOSIP.v5 trimers induce strong autologous tier-2 neutralizing antibody (NAb) responses in rabbits. In addition, the BG505 SOSIP.v6 trimers induced weak heterologous NAb responses against a subset of tier-2 viruses that were not elicited by the prototype BG505 SOSIP.664. These stabilization methods can be applied to trimers from multiple genotypes as components of multivalent vaccines aimed at inducing broadly NAbs (bNAbs).

2211-1247
1805-1817
Torrents de la Peña, Alba
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Julien, Jean Philippe
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de Taeye, Steven W.
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Garces, Fernando
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Guttman, Miklos
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Ozorowski, Gabriel
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Pritchard, Laura K.
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Behrens, Anna Janina
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Go, Eden P.
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Burger, Judith A.
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Schermer, Edith E.
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Sliepen, Kwinten
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Ketas, Thomas J.
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Pugach, Pavel
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Yasmeen, Anila
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Cottrell, Christopher A.
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Torres, Jonathan L.
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Vavourakis, Charlotte D.
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van Gils, Marit J.
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LaBranche, Celia
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Montefiori, David C.
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Desaire, Heather
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Crispin, Max
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Klasse, Per Johan
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Lee, Kelly K.
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Moore, John P.
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Ward, Andrew B.
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Wilson, Ian A.
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Sanders, Rogier W.
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Torrents de la Peña, Alba
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Julien, Jean Philippe
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de Taeye, Steven W.
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Garces, Fernando
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Guttman, Miklos
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Ozorowski, Gabriel
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Pritchard, Laura K.
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Behrens, Anna Janina
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Go, Eden P.
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Burger, Judith A.
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Schermer, Edith E.
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Sliepen, Kwinten
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Ketas, Thomas J.
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Pugach, Pavel
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Yasmeen, Anila
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Cottrell, Christopher A.
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Torres, Jonathan L.
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Vavourakis, Charlotte D.
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van Gils, Marit J.
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LaBranche, Celia
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Montefiori, David C.
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Desaire, Heather
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Crispin, Max
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Klasse, Per Johan
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Lee, Kelly K.
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Moore, John P.
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Ward, Andrew B.
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Wilson, Ian A.
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Sanders, Rogier W.
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Torrents de la Peña, Alba, Julien, Jean Philippe, de Taeye, Steven W., Garces, Fernando, Guttman, Miklos, Ozorowski, Gabriel, Pritchard, Laura K., Behrens, Anna Janina, Go, Eden P., Burger, Judith A., Schermer, Edith E., Sliepen, Kwinten, Ketas, Thomas J., Pugach, Pavel, Yasmeen, Anila, Cottrell, Christopher A., Torres, Jonathan L., Vavourakis, Charlotte D., van Gils, Marit J., LaBranche, Celia, Montefiori, David C., Desaire, Heather, Crispin, Max, Klasse, Per Johan, Lee, Kelly K., Moore, John P., Ward, Andrew B., Wilson, Ian A. and Sanders, Rogier W. (2017) Improving the immunogenicity of native-like HIV-1 envelope trimers by hyperstabilization. Cell Reports, 20 (8), 1805-1817. (doi:10.1016/j.celrep.2017.07.077).

Record type: Article

Abstract

The production of native-like recombinant versions of the HIV-1 envelope glycoprotein (Env) trimer requires overcoming the natural flexibility and instability of the complex. The engineered BG505 SOSIP.664 trimer mimics the structure and antigenicity of native Env. Here, we describe how the introduction of new disulfide bonds between the glycoprotein (gp)120 and gp41 subunits of SOSIP trimers of the BG505 and other genotypes improves their stability and antigenicity, reduces their conformational flexibility, and helps maintain them in the unliganded conformation. The resulting next-generation SOSIP.v5 trimers induce strong autologous tier-2 neutralizing antibody (NAb) responses in rabbits. In addition, the BG505 SOSIP.v6 trimers induced weak heterologous NAb responses against a subset of tier-2 viruses that were not elicited by the prototype BG505 SOSIP.664. These stabilization methods can be applied to trimers from multiple genotypes as components of multivalent vaccines aimed at inducing broadly NAbs (bNAbs).

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Accepted/In Press date: 26 July 2017
e-pub ahead of print date: 23 August 2017
Published date: August 2017
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Identifiers

Local EPrints ID: 414339
URI: http://eprints.soton.ac.uk/id/eprint/414339
DOI: doi:10.1016/j.celrep.2017.07.077
ISSN: 2211-1247
PURE UUID: 9d2c1273-6310-4762-9d0c-7bfd4d5ab8e5
ORCID for Max Crispin: ORCID iD orcid.org/0000-0002-1072-2694

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Date deposited: 26 Sep 2017 16:30
Last modified: 12 Jul 2024 01:58

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Contributors

Author: Alba Torrents de la Peña
Author: Jean Philippe Julien
Author: Steven W. de Taeye
Author: Fernando Garces
Author: Miklos Guttman
Author: Gabriel Ozorowski
Author: Laura K. Pritchard
Author: Anna Janina Behrens
Author: Eden P. Go
Author: Judith A. Burger
Author: Edith E. Schermer
Author: Kwinten Sliepen
Author: Thomas J. Ketas
Author: Pavel Pugach
Author: Anila Yasmeen
Author: Christopher A. Cottrell
Author: Jonathan L. Torres
Author: Charlotte D. Vavourakis
Author: Marit J. van Gils
Author: Celia LaBranche
Author: David C. Montefiori
Author: Heather Desaire
Author: Max Crispin ORCID iD
Author: Per Johan Klasse
Author: Kelly K. Lee
Author: John P. Moore
Author: Andrew B. Ward
Author: Ian A. Wilson
Author: Rogier W. Sanders

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