A multifunctional human monoclonal neutralizing antibody that targets a unique conserved epitope on influenza HA

Bangaru, Sandhya, Zhang, Heng, Gilchuk, Iuliia M., Voss, Thomas G., Irving, Ryan P., Gilchuk, Pavlo, Matta, Pranathi, Zhu, Xueyong, Lang, Shanshan, Nieusma, Travis, Richt, Juergen A., Albrecht, Randy A., Vanderven, Hillary A., Bombardi, Robin, Kent, Stephen J., Ward, Andrew B., Wilson, Ian A., and Crowe, James E. (2018) A multifunctional human monoclonal neutralizing antibody that targets a unique conserved epitope on influenza HA. Nature Communications, 9. 2669.

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Abstract

The high rate of antigenic drift in seasonal influenza viruses necessitates frequent changes in vaccine composition. Recent seasonal H3 vaccines do not protect against swine-origin H3N2 variant (H3N2v) strains that recently have caused severe human infections. Here, we report a human VH1-69 gene-encoded monoclonal antibody (mAb) designated H3v-47 that exhibits potent cross-reactive neutralization activity against human and swine H3N2 viruses that circulated since 1989. The crystal structure and electron microscopy reconstruction of H3v-47 Fab with the H3N2v hemagglutinin (HA) identify a unique epitope spanning the vestigial esterase and receptor-binding subdomains that is distinct from that of any known neutralizing antibody for influenza A H3 viruses. MAb H3v-47 functions largely by blocking viral egress from infected cells. Interestingly, H3v-47 also engages Fcγ receptor and mediates antibody dependent cellular cytotoxicity (ADCC). This newly identified conserved epitope can be used in design of novel immunogens for development of broadly protective H3 vaccines.

Item ID: 56895
Item Type: Article (Research - C1)
ISSN: 2041-1723
Copyright Information: 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/.
Funders: National Institutes of Health (NIH), National Cancer Institute (NCI), Clinical and Translational Science Award (CTSA)
Projects and Grants: NIH U19 AI117905, NIH contract NIH HHSN272201400024C, NCI Cancer Center Support Grant number P30 CA068485, CTSA award number UL1 TR000445
Date Deposited: 16 Jan 2019 07:43
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110705 Humoural Immunology and Immunochemistry @ 90%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 10%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
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