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Cell Rep. 2017 Dec 5;21(10):2992-3002. doi: 10.1016/j.celrep.2017.11.016.

Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains.

Author information

1
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA.
2
Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
3
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA. Electronic address: jmascola@nih.gov.
4
Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA. Electronic address: pdkwong@nih.gov.

Abstract

The elicitation of autologous neutralizing responses by immunization with HIV-1 envelope (Env) trimers conformationally stabilized in a prefusion closed state has generated considerable interest in the HIV-1 vaccine field. However, soluble prefusion closed Env trimers have been produced from only a handful of HIV-1 strains, limiting their utility as vaccine antigens and B cell probes. Here, we report the engineering from 81 HIV-1 strains of soluble, fully cleaved, prefusion Env trimers with appropriate antigenicity. We used a 96-well expression-screening format to assess the ability of artificial disulfides and Ile559Pro substitution (DS-SOSIP) to produce soluble cleaved-Env trimers; from 180 Env strains, 20 yielded prefusion closed trimers. We also created chimeras, by utilizing structure-based design to incorporate select regions from the well-behaved BG505 strain; from 180 Env strains, 78 DS-SOSIP-stabilized chimeras, including 61 additional strains, yielded prefusion closed trimers. Structure-based design thus enables the production of prefusion closed HIV-1-Env trimers from dozens of diverse strains.

KEYWORDS:

HIV-1 vaccine; conformational stabilization; envelope trimer; prefusion closed trimer; structure-based design

PMID:
29212041
DOI:
10.1016/j.celrep.2017.11.016
[Indexed for MEDLINE]
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