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TitleImmunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes.
Journal, issue, pagesCell, Vol. 163, Issue 7, Page 1702-1715, Year 2015
Publish dateDec 17, 2015
AuthorsSteven W de Taeye / Gabriel Ozorowski / Alba Torrents de la Peña / Miklos Guttman / Jean-Philippe Julien / Tom L G M van den Kerkhof / Judith A Burger / Laura K Pritchard / Pavel Pugach / Anila Yasmeen / Jordan Crampton / Joyce Hu / Ilja Bontjer / Jonathan L Torres / Heather Arendt / Joanne DeStefano / Wayne C Koff / Hanneke Schuitemaker / Dirk Eggink / Ben Berkhout / Hansi Dean / Celia LaBranche / Shane Crotty / Max Crispin / David C Montefiori / P J Klasse / Kelly K Lee / John P Moore / Ian A Wilson / Andrew B Ward / Rogier W Sanders /
PubMed AbstractThe 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. ...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.
External linksCell / PubMed:26687358 / PubMed Central
MethodsEM (single particle)
Resolution15.0 Å
Structure data

EMDB-6500:
Negative stain EM reconstruction of HIV-1 Env AMC008 SOSIP.v4 in complex with Fabs 35O22 and PGV04
Method: EM (single particle) / Resolution: 15.0 Å

Source
  • Human immunodeficiency virus 1
  • Homo sapiens (human)

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