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

Publication ,  Journal Article
Torrents de la Peña, A; Julien, J-P; de Taeye, SW; Garces, F; Guttman, M; Ozorowski, G; Pritchard, LK; Behrens, A-J; Go, EP; Burger, JA ...
Published in: Cell Rep
August 22, 2017

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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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

August 22, 2017

Volume

20

Issue

8

Start / End Page

1805 / 1817

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Rabbits
  • Humans
  • HIV-1
  • Animals
  • 31 Biological sciences
  • 1116 Medical Physiology
  • 0601 Biochemistry and Cell Biology
 

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Torrents de la Peña, A., Julien, J.-P., de Taeye, S. W., Garces, F., Guttman, M., Ozorowski, G., … Sanders, R. W. (2017). Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization. Cell Rep, 20(8), 1805–1817. https://doi.org/10.1016/j.celrep.2017.07.077
Torrents de la Peña, Alba, Jean-Philippe Julien, Steven W. de Taeye, Fernando Garces, Miklos Guttman, Gabriel Ozorowski, Laura K. Pritchard, et al. “Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization.Cell Rep 20, no. 8 (August 22, 2017): 1805–17. https://doi.org/10.1016/j.celrep.2017.07.077.
Torrents de la Peña A, Julien J-P, de Taeye SW, Garces F, Guttman M, Ozorowski G, et al. Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization. Cell Rep. 2017 Aug 22;20(8):1805–17.
Torrents de la Peña, Alba, et al. “Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization.Cell Rep, vol. 20, no. 8, Aug. 2017, pp. 1805–17. Pubmed, doi:10.1016/j.celrep.2017.07.077.
Torrents de la Peña A, Julien J-P, de Taeye SW, Garces F, Guttman M, Ozorowski G, Pritchard LK, Behrens A-J, Go EP, Burger JA, Schermer EE, Sliepen K, Ketas TJ, Pugach P, Yasmeen A, Cottrell CA, Torres JL, Vavourakis CD, van Gils MJ, LaBranche C, Montefiori DC, Desaire H, Crispin M, Klasse PJ, Lee KK, Moore JP, Ward AB, Wilson IA, Sanders RW. Improving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization. Cell Rep. 2017 Aug 22;20(8):1805–1817.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

August 22, 2017

Volume

20

Issue

8

Start / End Page

1805 / 1817

Location

United States

Related Subject Headings

  • env Gene Products, Human Immunodeficiency Virus
  • Rabbits
  • Humans
  • HIV-1
  • Animals
  • 31 Biological sciences
  • 1116 Medical Physiology
  • 0601 Biochemistry and Cell Biology