Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization
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).
- Authors:
-
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- 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
- Publication Date:
- Research Org.:
- Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS); SLAC National Accelerator Lab., Menlo Park, CA (United States). Stanford Synchrotron Radiation Lightsource (SSRL)
- Sponsoring Org.:
- 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)
- OSTI Identifier:
- 1499807
- Grant/Contract Number:
- P01 AI110657; CHAVI-ID UM1 AI100663; 2012041; THA-118628; ERC-StG-2011–280829-SHEV; OPP1084519; OPP1115782; AC02-76SF00515
- Resource Type:
- Journal Article: Accepted Manuscript
- Journal Name:
- Cell Reports
- Additional Journal Information:
- Journal Volume: 20; Journal Issue: 8; Journal ID: ISSN 2211-1247
- Publisher:
- Elsevier
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
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. Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization. United States: N. p., 2017.
Web. doi:10.1016/j.celrep.2017.07.077.
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. Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization. United States. https://doi.org/10.1016/j.celrep.2017.07.077
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". United States. https://doi.org/10.1016/j.celrep.2017.07.077. https://www.osti.gov/servlets/purl/1499807.
@article{osti_1499807,
title = {Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization},
author = {Torrents de la Peña, Alba and Julien, Jean-Philippe and de Taeye, Steven W. and Garces, Fernando and Guttman, Miklos and Ozorowski, Gabriel and Pritchard, Laura K. and Behrens, Anna-Janina and Go, Eden P. and Burger, Judith A. and Schermer, Edith E. and Sliepen, Kwinten and Ketas, Thomas J. and Pugach, Pavel and Yasmeen, Anila and Cottrell, Christopher A. and Torres, Jonathan L. and Vavourakis, Charlotte D. and van Gils, Marit J. and LaBranche, Celia and Montefiori, David C. and Desaire, Heather and Crispin, Max and Klasse, Per Johan and Lee, Kelly K. and Moore, John P. and Ward, Andrew B. and Wilson, Ian A. and Sanders, Rogier W.},
abstractNote = {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).},
doi = {10.1016/j.celrep.2017.07.077},
url = {https://www.osti.gov/biblio/1499807},
journal = {Cell Reports},
issn = {2211-1247},
number = 8,
volume = 20,
place = {United States},
year = {Tue Aug 22 00:00:00 EDT 2017},
month = {Tue Aug 22 00:00:00 EDT 2017}
}
Web of Science
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