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Broadly neutralizing antibodies targeting new sites of vulnerability in hepatitis C virus E1E2

Colbert, Michelle D. and Flyak, Andrew I. and Ogega, Clinton O. and Kinchen, Valerie J. and Massaccesi, Guido and Hernandez, Mayda and Davidson, Edgar and Doranz, Benjamin J. and Cox, Andrea L. and Crowe, James E., Jr. and Bailey, Justin R. (2019) Broadly neutralizing antibodies targeting new sites of vulnerability in hepatitis C virus E1E2. Journal of Virology, 93 (14). Art. No. e02070-18. ISSN 0022-538X. PMCID PMC6600205. doi:10.1128/jvi.02070-18.

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Increasing evidence indicates that broadly neutralizing antibodies (bNAbs) play an important role in immune-mediated control of hepatitis C virus (HCV) infection, but the relative contribution of neutralizing antibodies targeting antigenic sites across the HCV envelope (E1 and E2) proteins is unclear. Here, we isolated thirteen E1E2-specific monoclonal antibodies (MAbs) from B cells of a single HCV-infected individual who cleared one genotype 1a infection and then became persistently infected with a second genotype 1a strain. These MAbs bound six distinct discontinuous antigenic sites on the E1 protein, the E2 protein, or the E1E2 heterodimer. Three antigenic sites, designated AS108, AS112 (an N-terminal E1 site), and AS146, were distinct from previously described antigenic regions (ARs) 1 to 5 and E1 sites. Antibodies targeting four sites (AR3, AR4-5, AS108, and AS146) were broadly neutralizing. These MAbs also displayed distinct patterns of relative neutralizing potency (i.e., neutralization profiles) across a panel of diverse HCV strains, which led to complementary neutralizing breadth when they were tested in combination. Overall, this study demonstrates that HCV bNAb epitopes are not restricted to previously described antigenic sites, expanding the number of sites that could be targeted for vaccine development.

Item Type:Article
Related URLs:
URLURL TypeDescription CentralArticle
Flyak, Andrew I.0000-0002-8722-479X
Ogega, Clinton O.0000-0001-9700-1015
Kinchen, Valerie J.0000-0003-2317-9990
Massaccesi, Guido0000-0002-4528-0937
Davidson, Edgar0000-0002-3333-2314
Doranz, Benjamin J.0000-0002-8245-3083
Cox, Andrea L.0000-0002-9331-2462
Crowe, James E., Jr.0000-0002-0049-1079
Additional Information:© 2019 American Society for Microbiology. Received 21 November 2018; Accepted 1 May 2019; Accepted manuscript posted online 8 May 2019. We thank Brian G. Pierce for the use of his R code as well as Alexander Gooden and Jordan Salas for technical support. This research was supported by National Institutes of Health grants R01AI127469 (to J.R.B. and J.E.C.) and U19 AI088791 (to J.R.B.) and NIH contract HHSN272201400058C (to B.J.D.). A.I.F. is a Cancer Research Institute Irvington Fellow supported by the Cancer Research Institute. Content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Funding AgencyGrant Number
NIHU19 AI088791
Cancer Research InstituteUNSPECIFIED
Issue or Number:14
PubMed Central ID:PMC6600205
Record Number:CaltechAUTHORS:20190509-095314853
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Official Citation:Broadly Neutralizing Antibodies Targeting New Sites of Vulnerability in Hepatitis C Virus E1E2. Michelle D. Colbert, Andrew I. Flyak, Clinton O. Ogega, Valerie J. Kinchen, Guido Massaccesi, Mayda Hernandez, Edgar Davidson, Benjamin J. Doranz, Andrea L. Cox, James E. Crowe Jr., Justin R. Bailey. Journal of Virology Jun 2019, 93 (14) e02070-18; DOI: 10.1128/JVI.02070-18
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95368
Deposited By: Tony Diaz
Deposited On:09 May 2019 17:08
Last Modified:16 Nov 2021 17:12

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