Unique structural solution from a V(H)3-30 antibody targeting the hemagglutinin stem of influenza A viruses

Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by t...

Descripción completa

Detalles Bibliográficos
Autores principales: Harshbarger, Wayne D., Deming, Derrick, Lockbaum, Gordon J., Attatippaholkun, Nattapol, Kamkaew, Maliwan, Hou, Shurong, Somasundaran, Mohan, Wang, Jennifer P., Finberg, Robert W., Zhu, Quan Karen, Schiffer, Celia A., Marasco, Wayne A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835374/
https://www.ncbi.nlm.nih.gov/pubmed/33495478
http://dx.doi.org/10.1038/s41467-020-20879-6
_version_ 1783642511484387328
author Harshbarger, Wayne D.
Deming, Derrick
Lockbaum, Gordon J.
Attatippaholkun, Nattapol
Kamkaew, Maliwan
Hou, Shurong
Somasundaran, Mohan
Wang, Jennifer P.
Finberg, Robert W.
Zhu, Quan Karen
Schiffer, Celia A.
Marasco, Wayne A.
author_facet Harshbarger, Wayne D.
Deming, Derrick
Lockbaum, Gordon J.
Attatippaholkun, Nattapol
Kamkaew, Maliwan
Hou, Shurong
Somasundaran, Mohan
Wang, Jennifer P.
Finberg, Robert W.
Zhu, Quan Karen
Schiffer, Celia A.
Marasco, Wayne A.
author_sort Harshbarger, Wayne D.
collection PubMed
description Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among V(H)3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of V(H)3-30 antibodies and reveals that 3I14 represents a novel structural solution within the V(H)3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV.
format Online
Article
Text
id pubmed-7835374
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-78353742021-01-29 Unique structural solution from a V(H)3-30 antibody targeting the hemagglutinin stem of influenza A viruses Harshbarger, Wayne D. Deming, Derrick Lockbaum, Gordon J. Attatippaholkun, Nattapol Kamkaew, Maliwan Hou, Shurong Somasundaran, Mohan Wang, Jennifer P. Finberg, Robert W. Zhu, Quan Karen Schiffer, Celia A. Marasco, Wayne A. Nat Commun Article Broadly neutralizing antibodies (bnAbs) targeting conserved influenza A virus (IAV) hemagglutinin (HA) epitopes can provide valuable information for accelerating universal vaccine designs. Here, we report structural details for heterosubtypic recognition of HA from circulating and emerging IAVs by the human antibody 3I14. Somatic hypermutations play a critical role in shaping the HCDR3, which alone and uniquely among V(H)3-30 derived antibodies, forms contacts with five sub-pockets within the HA-stem hydrophobic groove. 3I14 light-chain interactions are also key for binding HA and contribute a large buried surface area spanning two HA protomers. Comparison of 3I14 to bnAbs from several defined classes provide insights to the bias selection of V(H)3-30 antibodies and reveals that 3I14 represents a novel structural solution within the V(H)3-30 repertoire. The structures reported here improve our understanding of cross-group heterosubtypic binding activity, providing the basis for advancing immunogen designs aimed at eliciting a broadly protective response to IAV. Nature Publishing Group UK 2021-01-25 /pmc/articles/PMC7835374/ /pubmed/33495478 http://dx.doi.org/10.1038/s41467-020-20879-6 Text en © The Author(s) 2021 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/.
spellingShingle Article
Harshbarger, Wayne D.
Deming, Derrick
Lockbaum, Gordon J.
Attatippaholkun, Nattapol
Kamkaew, Maliwan
Hou, Shurong
Somasundaran, Mohan
Wang, Jennifer P.
Finberg, Robert W.
Zhu, Quan Karen
Schiffer, Celia A.
Marasco, Wayne A.
Unique structural solution from a V(H)3-30 antibody targeting the hemagglutinin stem of influenza A viruses
title Unique structural solution from a V(H)3-30 antibody targeting the hemagglutinin stem of influenza A viruses
title_full Unique structural solution from a V(H)3-30 antibody targeting the hemagglutinin stem of influenza A viruses
title_fullStr Unique structural solution from a V(H)3-30 antibody targeting the hemagglutinin stem of influenza A viruses
title_full_unstemmed Unique structural solution from a V(H)3-30 antibody targeting the hemagglutinin stem of influenza A viruses
title_short Unique structural solution from a V(H)3-30 antibody targeting the hemagglutinin stem of influenza A viruses
title_sort unique structural solution from a v(h)3-30 antibody targeting the hemagglutinin stem of influenza a viruses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835374/
https://www.ncbi.nlm.nih.gov/pubmed/33495478
http://dx.doi.org/10.1038/s41467-020-20879-6
work_keys_str_mv AT harshbargerwayned uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses
AT demingderrick uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses
AT lockbaumgordonj uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses
AT attatippaholkunnattapol uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses
AT kamkaewmaliwan uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses
AT houshurong uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses
AT somasundaranmohan uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses
AT wangjenniferp uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses
AT finbergrobertw uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses
AT zhuquankaren uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses
AT schifferceliaa uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses
AT marascowaynea uniquestructuralsolutionfromavh330antibodytargetingthehemagglutininstemofinfluenzaaviruses

Ejemplares similares