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

  1. Author:
    Joyce, M Gordon
    Georgiev, Ivelin S
    Yang, Yongping
    Druz, Aliaksandr
    Geng, Hui
    Chuang, Gwo-Yu
    Kwon, Young Do
    Pancera, Marie
    Rawi, Reda
    Sastry, Mallika
    Stewart-Jones, Guillaume B E
    Zheng, Angela
    Zhou, Tongqing
    Choe, Misook
    Van Galen, Joseph G
    Chen, Rita E
    Lees, Christopher R
    Narpala, Sandeep
    Chambers, Michael
    Tsybovsky, Yaroslav
    Baxa, Ulrich
    McDermott, Adrian B
    Mascola, John R
    Kwong, Peter D

  2. Author Address

    Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA., Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA. Electronic address: jmascola@nih.gov., Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, MD 20892-3005, USA. Electronic address: pdkwong@nih.gov.,
    1. Year: 2017
    2. Date: Dec 05
  2. Journal: Cell reports
    1. 21
    2. 10
    3. Pages: 2992-3002
  4. Type of Article: Article
  1. 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. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2017.11.016
  3. PMID: 29212041
  4. View record in Web of Science®
  5. WOS: 000417146000030
  6. PII : S2211-1247(17)31636-4

Library Notes

  1. Fiscal Year: FY2017-2018
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