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

Ahmed A. Quadeer, Raymond H. Y. Louie and Matthew R. McKay ()
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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
Matthew R. McKay: The Hong Kong University of Science and Technology, Clear Water Bay

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-09819-1

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