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Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals

Despite recent success in hepatitis C virus (HCV) treatment using antivirals, an HCV vaccine is still needed to prevent reinfections in treated patients, to avert the emergence of drug-resistant strains, and to provide protection for people with no access to the antiviral therapeutics. The early pro...

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Autores principales: Bozhanova, Nina G., Flyak, Andrew I., Brown, Benjamin P., Ruiz, Stormy E., Salas, Jordan, Rho, Semi, Bombardi, Robin G., Myers, Luke, Soto, Cinque, Bailey, Justin R., Crowe, James E., Bjorkman, Pamela J., Meiler, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177688/
https://www.ncbi.nlm.nih.gov/pubmed/35676279
http://dx.doi.org/10.1038/s41467-022-30865-9
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author Bozhanova, Nina G.
Flyak, Andrew I.
Brown, Benjamin P.
Ruiz, Stormy E.
Salas, Jordan
Rho, Semi
Bombardi, Robin G.
Myers, Luke
Soto, Cinque
Bailey, Justin R.
Crowe, James E.
Bjorkman, Pamela J.
Meiler, Jens
author_facet Bozhanova, Nina G.
Flyak, Andrew I.
Brown, Benjamin P.
Ruiz, Stormy E.
Salas, Jordan
Rho, Semi
Bombardi, Robin G.
Myers, Luke
Soto, Cinque
Bailey, Justin R.
Crowe, James E.
Bjorkman, Pamela J.
Meiler, Jens
author_sort Bozhanova, Nina G.
collection PubMed
description Despite recent success in hepatitis C virus (HCV) treatment using antivirals, an HCV vaccine is still needed to prevent reinfections in treated patients, to avert the emergence of drug-resistant strains, and to provide protection for people with no access to the antiviral therapeutics. The early production of broadly neutralizing antibodies (bNAbs) associates with HCV clearance. Several potent bNAbs bind a conserved HCV glycoprotein E2 epitope using an unusual heavy chain complementarity determining region 3 (HCDR3) containing an intra-loop disulfide bond. Isolation of additional structurally-homologous bNAbs would facilitate the recognition of key determinants of such bNAbs and guide rational vaccine design. Here we report the identification of new antibodies containing an HCDR3 disulfide bond motif using computational screening with the Rosetta software. Using the newly-discovered and already-known members of this antibody family, we review the required HCDR3 amino acid composition and propose determinants for the bent versus straight HCDR3 loop conformation observed in these antibodies.
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spelling pubmed-91776882022-06-10 Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals Bozhanova, Nina G. Flyak, Andrew I. Brown, Benjamin P. Ruiz, Stormy E. Salas, Jordan Rho, Semi Bombardi, Robin G. Myers, Luke Soto, Cinque Bailey, Justin R. Crowe, James E. Bjorkman, Pamela J. Meiler, Jens Nat Commun Article Despite recent success in hepatitis C virus (HCV) treatment using antivirals, an HCV vaccine is still needed to prevent reinfections in treated patients, to avert the emergence of drug-resistant strains, and to provide protection for people with no access to the antiviral therapeutics. The early production of broadly neutralizing antibodies (bNAbs) associates with HCV clearance. Several potent bNAbs bind a conserved HCV glycoprotein E2 epitope using an unusual heavy chain complementarity determining region 3 (HCDR3) containing an intra-loop disulfide bond. Isolation of additional structurally-homologous bNAbs would facilitate the recognition of key determinants of such bNAbs and guide rational vaccine design. Here we report the identification of new antibodies containing an HCDR3 disulfide bond motif using computational screening with the Rosetta software. Using the newly-discovered and already-known members of this antibody family, we review the required HCDR3 amino acid composition and propose determinants for the bent versus straight HCDR3 loop conformation observed in these antibodies. Nature Publishing Group UK 2022-06-08 /pmc/articles/PMC9177688/ /pubmed/35676279 http://dx.doi.org/10.1038/s41467-022-30865-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bozhanova, Nina G.
Flyak, Andrew I.
Brown, Benjamin P.
Ruiz, Stormy E.
Salas, Jordan
Rho, Semi
Bombardi, Robin G.
Myers, Luke
Soto, Cinque
Bailey, Justin R.
Crowe, James E.
Bjorkman, Pamela J.
Meiler, Jens
Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals
title Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals
title_full Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals
title_fullStr Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals
title_full_unstemmed Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals
title_short Computational identification of HCV neutralizing antibodies with a common HCDR3 disulfide bond motif in the antibody repertoires of infected individuals
title_sort computational identification of hcv neutralizing antibodies with a common hcdr3 disulfide bond motif in the antibody repertoires of infected individuals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9177688/
https://www.ncbi.nlm.nih.gov/pubmed/35676279
http://dx.doi.org/10.1038/s41467-022-30865-9
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