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Identifying immunologically-vulnerable regions of the HCV E2 glycoprotein and broadly neutralizing antibodies that target them

Author

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  • Ahmed A. Quadeer

    (The Hong Kong University of Science and Technology, Clear Water Bay)

  • Raymond H. Y. Louie

    (The Hong Kong University of Science and Technology, Clear Water Bay
    The Hong Kong University of Science and Technology, Clear Water Bay
    University of New South Wales
    University of New South Wales)

  • Matthew R. McKay

    (The Hong Kong University of Science and Technology, Clear Water Bay
    The Hong Kong University of Science and Technology, Clear Water Bay)

Abstract

Isolation of broadly neutralizing human monoclonal antibodies (HmAbs) targeting the E2 glycoprotein of Hepatitis C virus (HCV) has sparked hope for effective vaccine development. Nonetheless, escape mutations have been reported. Ideally, a potent vaccine should elicit HmAbs that target regions of E2 that are most difficult to escape. Here, aimed at addressing this challenge, we develop a predictive in-silico evolutionary model for E2 that identifies one such region, a specific antigenic domain, making it an attractive target for a robust antibody response. Specific broadly neutralizing HmAbs that appear difficult to escape from are also identified. By providing a framework for identifying vulnerable regions of E2 and for assessing the potency of specific antibodies, our results can aid the rational design of an effective prophylactic HCV vaccine.

Suggested Citation

  • Ahmed A. Quadeer & Raymond H. Y. Louie & Matthew R. McKay, 2019. "Identifying immunologically-vulnerable regions of the HCV E2 glycoprotein and broadly neutralizing antibodies that target them," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-09819-1
    DOI: 10.1038/s41467-019-09819-1
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    Cited by:

    1. Avik Biswas & Allan Haldane & Ronald M Levy, 2022. "Limits to detecting epistasis in the fitness landscape of HIV," PLOS ONE, Public Library of Science, vol. 17(1), pages 1-22, January.

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