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Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation

  1. Author:
    Zhou, Tongqing
    Doria-Rose, Nicole A
    Cheng, Cheng
    Stewart-Jones, Guillaume B E
    Chuang, Gwo-Yu
    Chambers, Michael
    Druz, Aliaksandr
    Geng, Hui
    McKee, Krisha
    Kwon, Young Do
    O'Dell, Sijy
    Sastry, Mallika
    Schmidt, Stephen D
    Xu, Kai
    Chen, Lei
    Chen, Rita E
    Louder, Mark K
    Pancera, Marie
    Wanninger, Timothy G
    Zhang, Baoshan
    Zheng, Anqi
    Farney, S Katie
    Foulds, Kathryn E
    Georgiev, Ivelin S
    Joyce, M Gordon
    Lemmin, Thomas
    Narpala, Sandeep
    Rawi, Reda
    Soto, Cinque
    Todd, John-Paul
    Shen, Chen-Hsiang
    Tsybovsky, Yaroslav
    Yang, Yongping
    Zhao, Peng
    Haynes, Barton F
    Stamatatos, Leonidas
    Tiemeyer, Michael
    Wells, Lance
    Scorpio, Diana G
    Shapiro, Lawrence
    McDermott, Adrian B
    Mascola, John R
    Kwong, Peter D

  2. Author Address

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702-1201, USA., Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA; Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA., Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA., Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, P.O. Box 19024, Seattle, WA 98109, USA., Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jmascola@nih.gov., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA. Electronic address: pdkwong@nih.gov.,
    1. Year: 2017
    2. Date: Apr 25
  2. Journal: Cell Reports
    1. 19
    2. 4
    3. Pages: 719-732
  4. Type of Article: Article
  1. Abstract:

    While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID50) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies. Published by Elsevier Inc.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.celrep.2017.04.013
  3. PMID: 28445724
  4. View record in Web of Science®
  5. WOS: 000401133700007

Library Notes

  1. Fiscal Year: FY2016-2017
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