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

TitleImproving the Immunogenicity of Native-like HIV-1 Envelope Trimers by Hyperstabilization.
Publication TypeJournal Article
Year of Publication2017
AuthorsA de la Peña T, 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 P J, Lee KK, Moore JP, Ward AB, Wilson IA, Sanders RW
JournalCell Rep
Volume20
Issue8
Pagination1805-1817
Date Published08/22/2017
ISSN2211-1247
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).

DOI10.1016/j.celrep.2017.07.077
Alternate JournalCell Rep
PubMed ID28834745
Grant ListUM1 AI100663 / AI / NIAID NIH HHS / United States
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