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Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody

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  • Tianlei Ying

    (Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College, Fudan University)

  • Ponraj Prabakaran

    (Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health
    Present address: Sanofi Pasteur Biologics, Cambridge, Massachusetts 02139, USA.)

  • Lanying Du

    (Lindsley F. Kimball Research Institute, New York Blood Center)

  • Wei Shi

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Yang Feng

    (Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Yanping Wang

    (Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Lingshu Wang

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

  • Wei Li

    (Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College, Fudan University
    Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Shibo Jiang

    (Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College, Fudan University
    Lindsley F. Kimball Research Institute, New York Blood Center)

  • Dimiter S. Dimitrov

    (Protein Interactions Section, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health)

  • Tongqing Zhou

    (Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health)

Abstract

The MERS-CoV is an emerging virus, which already infected more than 1,300 humans with high (∼36%) mortality. Here, we show that m336, an exceptionally potent human anti-MERS-CoV antibody, is almost germline with only one somatic mutation in the heavy chain. The structure of Fab m336 in complex with the MERS-CoV receptor-binding domain reveals that its IGHV1-69-derived heavy chain provides more than 85% binding surface and that its epitope almost completely overlaps with the receptor-binding site. Analysis of antibodies from 69 healthy humans suggests an important role of the V(D)J recombination-generated junctional and allele-specific residues for achieving high affinity of binding at such low levels of somatic hypermutation. Our results also have important implications for development of vaccine immunogens based on the newly identified m336 epitope as well as for elucidation of mechanisms of neutralization by m336-like antibodies and their elicitation in vivo.

Suggested Citation

  • Tianlei Ying & Ponraj Prabakaran & Lanying Du & Wei Shi & Yang Feng & Yanping Wang & Lingshu Wang & Wei Li & Shibo Jiang & Dimiter S. Dimitrov & Tongqing Zhou, 2015. "Junctional and allele-specific residues are critical for MERS-CoV neutralization by an exceptionally potent germline-like antibody," Nature Communications, Nature, vol. 6(1), pages 1-10, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9223
    DOI: 10.1038/ncomms9223
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    Cited by:

    1. Nina G. Bozhanova & Andrew I. Flyak & Benjamin P. Brown & Stormy E. Ruiz & Jordan Salas & Semi Rho & Robin G. Bombardi & Luke Myers & Cinque Soto & Justin R. Bailey & James E. Crowe & Pamela J. Bjorkm, 2022. "Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Kun-Wei Chan & Christina C. Luo & Hong Lu & Xueling Wu & Xiang-Peng Kong, 2021. "A site of vulnerability at V3 crown defined by HIV-1 bNAb M4008_N1," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

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