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Vaccine elicitation and structural basis for antibody protection against alphaviruses

  1. Author:
    Sutton, Matthew S
    Pletnev, Sergei
    Callahan, Victoria
    Ko, Sungyoul
    Tsybovsky,Yaroslav
    Bylund, Tatsiana
    Casner, Ryan G
    Cerutti, Gabriele
    Gardner, Christina L
    Guirguis, Veronica
    Verardi, Raffaello
    Zhang, Baoshan
    Ambrozak, David
    Beddall, Margaret
    Lei, Hong
    Yang, Eun Sung
    Liu, Tracy
    Henry, Amy R
    Rawi, Reda
    Schön, Arne
    Schramm, Chaim A
    Shen, Chen-Hsiang
    Shi, Wei
    Stephens,Tyler
    Yang, Yongping
    Florez, Maria Burgos
    Ledgerwood, Julie E
    Burke, Crystal W
    Shapiro, Lawrence
    Fox, Julie M
    Kwong, Peter D
    Roederer, Mario

  2. Author Address

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Vaccine Research Center Electron Microscopy Unit, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA., Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA., Virology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD 21702, USA., Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA., Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10027, USA; Department of Biochemistry and Molecular Biophysics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA; Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, 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 Vagelos College of Physicians and Surgeons, New York, NY 10032, USA. Electronic address: pdkwong@nih.gov., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: roederer@nih.gov.,
    1. Year: 2023
    2. Date: Jun 08
    3. Epub Date: 2023 06 08
  2. Journal: Cell
    1. 186
    2. 12
    3. Pages: 2672-2689.e25
  4. Type of Article: Article
  1. Abstract:

    Alphaviruses are RNA viruses that represent emerging public health threats. To identify protective antibodies, we immunized macaques with a mixture of western, eastern, and Venezuelan equine encephalitis virus-like particles (VLPs), a regimen that protects against aerosol challenge with all three viruses. Single- and triple-virus-specific antibodies were isolated, and we identified 21 unique binding groups. Cryo-EM structures revealed that broad VLP binding inversely correlated with sequence and conformational variability. One triple-specific antibody, SKT05, bound proximal to the fusion peptide and neutralized all three Env-pseudotyped encephalitic alphaviruses by using different symmetry elements for recognition across VLPs. Neutralization in other assays (e.g., chimeric Sindbis virus) yielded variable results. SKT05 bound backbone atoms of sequence-diverse residues, enabling broad recognition despite sequence variability; accordingly, SKT05 protected mice against Venezuelan equine encephalitis virus, chikungunya virus, and Ross River virus challenges. Thus, a single vaccine-elicited antibody can protect in vivo against a broad range of alphaviruses. Published by Elsevier Inc.

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External Sources

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  2. DOI: 10.1016/j.cell.2023.05.019
  3. PMID: 37295404
  4. PII : S0092-8674(23)00538-X

Library Notes

  1. Fiscal Year: FY2022-2023
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