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TitleStructure-based design of native-like HIV-1 envelope trimers to silence non-neutralizing epitopes and eliminate CD4 binding.
Journal, issue, pagesNat Commun, Vol. 8, Issue 1, Page 1655, Year 2017
Publish dateNov 21, 2017
AuthorsDaniel W Kulp / Jon M Steichen / Matthias Pauthner / Xiaozhen Hu / Torben Schiffner / Alessia Liguori / Christopher A Cottrell / Colin Havenar-Daughton / Gabriel Ozorowski / Erik Georgeson / Oleksandr Kalyuzhniy / Jordan R Willis / Michael Kubitz / Yumiko Adachi / Samantha M Reiss / Mia Shin / Natalia de Val / Andrew B Ward / Shane Crotty / Dennis R Burton / William R Schief /
PubMed AbstractElicitation of broadly neutralizing antibodies (bnAbs) is a primary HIV vaccine goal. Native-like trimers mimicking virion-associated spikes present nearly all bnAb epitopes and are therefore ...Elicitation of broadly neutralizing antibodies (bnAbs) is a primary HIV vaccine goal. Native-like trimers mimicking virion-associated spikes present nearly all bnAb epitopes and are therefore promising vaccine antigens. However, first generation native-like trimers expose epitopes for non-neutralizing antibodies (non-nAbs), which may hinder bnAb induction. We here employ computational and structure-guided design to develop improved native-like trimers that reduce exposure of non-nAb epitopes in the V3-loop and trimer base, minimize both CD4 reactivity and CD4-induced non-nAb epitope exposure, and increase thermal stability while maintaining bnAb antigenicity. In rabbit immunizations with native-like trimers of the 327c isolate, improved trimers suppress elicitation of V3-directed and tier-1 neutralizing antibodies and induce robust autologous tier-2 neutralization, unlike a first-generation trimer. The improved native-like trimers from diverse HIV isolates, and the design methods, have promise to assist in the development of a HIV vaccine.
External linksNat Commun / PubMed:29162799 / PubMed Central
MethodsEM (single particle)
Resolution25.0 Å
Structure data

EMDB-9402:
BG505 SOSIPv4.1 with rabbit Fab 12N
Method: EM (single particle) / Resolution: 25.0 Å

Source
  • Homo sapiens (human)

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