Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization

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.; Sanders, Rogier W.

doi:10.1016/j.celrep.2017.07.077

Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization

Journal Article · Tue Aug 22 04:00:00 EDT 2017 · Cell Reports

DOI:https://doi.org/10.1016/j.celrep.2017.07.077· OSTI ID:1499807

Torrents de la Peña, Alba ^[1]; Julien, Jean-Philippe ^[2]; de Taeye, Steven W. ^[1]; Garces, Fernando ^[3]; Guttman, Miklos ^[4]; Ozorowski, Gabriel ^[5]; Pritchard, Laura K. ^[6]; Behrens, Anna-Janina ^[6]; Go, Eden P. ^[7]; Burger, Judith A. ^[1]; Schermer, Edith E. ^[1]; Sliepen, Kwinten ^[1]; Ketas, Thomas J. ^[8]; Pugach, Pavel ^[8]; Yasmeen, Anila ^[8]; Cottrell, Christopher A. ^[5]; Torres, Jonathan L. ^[5]; Vavourakis, Charlotte D. ^[1]; van Gils, Marit J. ^[1]; LaBranche, Celia ^[9] more »

Univ. of Amsterdam (Netherlands)
The Scripps Research Inst., La Jolla, CA (United States); The Hospital for Sick Children Research Inst., Toronto, ON (Canada); Univ. of Toronto, ON (Canada)
The Scripps Research Inst., La Jolla, CA (United States); Amgen, Inc., Thousand Oaks, CA (United States)
Univ. of Washington, Seattle, WA (United States)
The Scripps Research Inst., La Jolla, CA (United States)
Univ. of Oxford (United Kingdom)
Univ. of Kansas, Lawrence, KS (United States)
Cornell Univ., Ithaca, NY (United States). Weill Medical College
Duke Univ. Medical Center, Durham, NC (United States)
Univ. of Amsterdam (Netherlands); Cornell Univ., Ithaca, NY (United States). Weill Medical College

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).

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS); SLAC National Accelerator Laboratory, Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)

Sponsoring Organization:: National Institutes of Health (NIH); The Scripps Research Institute; International AIDS Vaccine Initiative (IAVI); Aids fonds Netherlands; Canadian Institutes of Health Research (CIHR); Netherlands Organization for Scientific Research (NWO); European Research Council (ERC); Collaboration for AIDS Vaccine Discovery (CAVD); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1499807

Journal Information:: Cell Reports, Journal Name: Cell Reports Journal Issue: 8 Vol. 20; ISSN 2211-1247

Publisher:: ElsevierCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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