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Broadly Neutralizing Antibody Mediated Clearance of Human Hepatitis C Virus Infection

ARTICLE: Broadly Neutralizing Antibody Mediated Clearance of Human Hepatitis C Virus Infection

AUTHORS: Valerie J. Kinchen, Muhammad N. Zahid, Andrew I. Flyak, Mary G. Soliman, Gerald H. Learn, Shuyi Wang, Edgar Davidson, Benjamin J. Doranz, Stuart C. Ray, Andrea L. Cox, James E. Crowe Jr., Pamela J. Bjorkman, George M. Shaw, Justin R. Bailey

JOURNAL: Cell Host Microbe. 2018 Nov 14;24(5):717-730.e5. doi: 10.1016/j.chom.2018.10.012.


The role that broadly neutralizing antibodies (bNAbs) play in natural clearance of human hepatitis C virus (HCV) infection and the underlying mechanisms remain unknown. Here, we investigate the mechanism by which bNAbs, isolated from two humans who spontaneously cleared HCV infection, contribute to HCV control. Using viral gene sequences amplified from longitudinal plasma of the two subjects, we found that these bNAbs, which target the front layer of the HCV envelope protein E2, neutralized most autologous HCV strains. Acquisition of resistance to bNAbs by some autologous strains was accompanied by progressive loss of E2 protein function, and temporally associated with HCV clearance. These data demonstrate that bNAbs can mediate clearance of human HCV infection by neutralizing infecting strains and driving escaped viruses to an unfit state. These immunopathologic events distinguish HCV from HIV-1 and suggest that development of an HCV vaccine may be achievable.

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Related article: HCV Broadly Neutralizing Antibodies Use a CDRH3 Disulfide Motif to Recognize an E2 Glycoprotein Site that Can Be Targeted for Vaccine Design


Kelsey Bennett