| Literature DB >> 26687358 |
Steven W de Taeye1, Gabriel Ozorowski2, Alba Torrents de la Peña1, Miklos Guttman3, Jean-Philippe Julien2, Tom L G M van den Kerkhof4, Judith A Burger1, Laura K Pritchard5, Pavel Pugach6, Anila Yasmeen6, Jordan Crampton7, Joyce Hu7, Ilja Bontjer1, Jonathan L Torres2, Heather Arendt8, Joanne DeStefano8, Wayne C Koff8, Hanneke Schuitemaker9, Dirk Eggink1, Ben Berkhout1, Hansi Dean8, Celia LaBranche10, Shane Crotty7, Max Crispin5, David C Montefiori10, P J Klasse6, Kelly K Lee3, John P Moore6, Ian A Wilson11, Andrew B Ward2, Rogier W Sanders12.
Abstract
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.Entities:
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Year: 2015 PMID： 26687358 PMCID： PMC4732737 DOI： 10.1016/j.cell.2015.11.056
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582