Broadly Neutralizing Antibody Mediated Clearance of Human Hepatitis C Virus Infection

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, Pamela J. Bjorkman, George M. Shaw, Justin R. Bailey

Research output: Contribution to journalArticle

Abstract

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. Kinchen et al. demonstrate that antibodies isolated from humans who spontaneously cleared HCV infection blocked many different HCV strains. Viruses that evolved resistance to these antibodies lost the ability to replicate, suggesting that antibodies are important for HCV clearance, and an HCV vaccine may be attainable.

Original languageEnglish (US)
Pages (from-to)717-730.e5
JournalCell Host and Microbe
Volume24
Issue number5
DOIs
StatePublished - Nov 14 2018

Keywords

  • HCV clearance
  • antibody specificity
  • binding sites
  • hepatitis C virus
  • immunologic memory
  • neutralizing antibodies

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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  • Cite this

    Kinchen, V. J., Zahid, M. N., Flyak, A. I., Soliman, M. G., Learn, G. H., Wang, S., Davidson, E., Doranz, B. J., Ray, S. C., Cox, A. L., Crowe, J. E., Bjorkman, P. J., Shaw, G. M., & Bailey, J. R. (2018). Broadly Neutralizing Antibody Mediated Clearance of Human Hepatitis C Virus Infection. Cell Host and Microbe, 24(5), 717-730.e5. https://doi.org/10.1016/j.chom.2018.10.012