Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes.

Published

Journal Article

The envelope glycoprotein trimer mediates HIV-1 entry into cells. The trimer is flexible, fluctuating between closed and more open conformations and sometimes sampling the fully open, CD4-bound form. We hypothesized that conformational flexibility and transient exposure of non-neutralizing, immunodominant epitopes could hinder the induction of broadly neutralizing antibodies (bNAbs). We therefore modified soluble Env trimers to stabilize their closed, ground states. The trimer variants were indeed stabilized in the closed conformation, with a reduced ability to undergo receptor-induced conformational changes and a decreased exposure of non-neutralizing V3-directed antibody epitopes. In rabbits, the stabilized trimers induced similar autologous Tier-1B or Tier-2 NAb titers to those elicited by the corresponding wild-type trimers but lower levels of V3-directed Tier-1A NAbs. Stabilized, closed trimers might therefore be useful components of vaccines aimed at inducing bNAbs.

Full Text

Duke Authors

Cited Authors

  • de Taeye, SW; Ozorowski, G; Torrents de la Peña, A; Guttman, M; Julien, J-P; van den Kerkhof, TLGM; Burger, JA; Pritchard, LK; Pugach, P; Yasmeen, A; Crampton, J; Hu, J; Bontjer, I; Torres, JL; Arendt, H; DeStefano, J; Koff, WC; Schuitemaker, H; Eggink, D; Berkhout, B; Dean, H; LaBranche, C; Crotty, S; Crispin, M; Montefiori, DC; Klasse, PJ; Lee, KK; Moore, JP; Wilson, IA; Ward, AB; Sanders, RW

Published Date

  • December 2015

Published In

Volume / Issue

  • 163 / 7

Start / End Page

  • 1702 - 1715

PubMed ID

  • 26687358

Pubmed Central ID

  • 26687358

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2015.11.056

Language

  • eng