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Article: An IgM antibody targeting the receptor binding site of influenza B blocks viral infection with great breadth and potency

TitleAn IgM antibody targeting the receptor binding site of influenza B blocks viral infection with great breadth and potency
Authors
Keywordsinfluenza B virus
hemagglutinin
receptor binding site
broadly neutralizing antibodies
IgM
Issue Date2019
PublisherIvyspring International Publisher. The Journal's web site is located at http://www.thno.org/
Citation
Theranostics, 2019, v. 9 n. 1, p. 210-231 How to Cite?
AbstractBroadly neutralizing antibodies (bnAbs) targeting the receptor binding site (RBS) of hemagglutinin (HA) have potential for developing into powerful anti-influenza agents. Several previously reported influenza B bnAbs are nevertheless unable to neutralize a portion of influenza B virus variants. HA-specific bnAbs with hemagglutination inhibition (HI) activity may possess the ability to block virus entry directly. Polymeric IgM antibodies are expected to more effectively inhibit virus attachment and entry into target cells due to their higher avidity and/or steric hindrance. We therefore hypothesized that certain RBS-targeted IgM antibodies with strong cross-lineage HI activity might display broader and more potent antiviral activity against rapidly evolving influenza B viruses. Methods: In this study, we generated IgM and IgG bnAbs targeting the RBS of influenza B virus using the murine hybridoma technique. IgM and IgG versions of the same antibodies were then developed by isotype switching and characterized in subsequent in vitro and in vivo experiments. Results: Two IgM and two IgG bnAbs against influenza B virus HA were identified. Of these, one IgM subtype antibody, C7G6-IgM, showed strong HI and neutralization activities against all 20 representative influenza B strains tested, with higher potency and broader breadth of anti-influenza activity in vitro than the IgG subtype variant of itself, or other previously-reported influenza B bnAbs. Furthermore, C7G6-IgM conferred excellent cross-protection against distinct lineages of influenza B viruses in mice and ferrets, performing better than the anti-influenza drug oseltamivir, and showed an additive antiviral effect when administered in combination with oseltamivir. Mechanistically, C7G6-IgM potently inhibits infection with influenza B virus strains from different lineages by blocking viral entry. Conclusion: In summary, our study highlights the potential of IgM subtype antibodies in combatting pathogenic microbes. Moreover, C7G6-IgM is a promising candidate for the development of prophylactics or therapeutics against influenza B infection.
Persistent Identifierhttp://hdl.handle.net/10722/272005
ISSN
2017 Impact Factor: 8.537
2015 SCImago Journal Rankings: 2.702
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorShen, C-
dc.contributor.authorZhang, M-
dc.contributor.authorChen, Y-
dc.contributor.authorZhang, L-
dc.contributor.authorWang, G-
dc.contributor.authorChen, J-
dc.contributor.authorChen, S-
dc.contributor.authorLi, Z-
dc.contributor.authorWei, F-
dc.contributor.authorChen, J-
dc.contributor.authorYang, K-
dc.contributor.authorGuo, S-
dc.contributor.authorWang, Y-
dc.contributor.authorZheng, Q-
dc.contributor.authorYu, H-
dc.contributor.authorLuo, W-
dc.contributor.authorZhang, J-
dc.contributor.authorChen, H-
dc.contributor.authorChen, Y-
dc.contributor.authorXia, N-
dc.date.accessioned2019-07-20T10:33:50Z-
dc.date.available2019-07-20T10:33:50Z-
dc.date.issued2019-
dc.identifier.citationTheranostics, 2019, v. 9 n. 1, p. 210-231-
dc.identifier.issn1838-7640-
dc.identifier.urihttp://hdl.handle.net/10722/272005-
dc.description.abstractBroadly neutralizing antibodies (bnAbs) targeting the receptor binding site (RBS) of hemagglutinin (HA) have potential for developing into powerful anti-influenza agents. Several previously reported influenza B bnAbs are nevertheless unable to neutralize a portion of influenza B virus variants. HA-specific bnAbs with hemagglutination inhibition (HI) activity may possess the ability to block virus entry directly. Polymeric IgM antibodies are expected to more effectively inhibit virus attachment and entry into target cells due to their higher avidity and/or steric hindrance. We therefore hypothesized that certain RBS-targeted IgM antibodies with strong cross-lineage HI activity might display broader and more potent antiviral activity against rapidly evolving influenza B viruses. Methods: In this study, we generated IgM and IgG bnAbs targeting the RBS of influenza B virus using the murine hybridoma technique. IgM and IgG versions of the same antibodies were then developed by isotype switching and characterized in subsequent in vitro and in vivo experiments. Results: Two IgM and two IgG bnAbs against influenza B virus HA were identified. Of these, one IgM subtype antibody, C7G6-IgM, showed strong HI and neutralization activities against all 20 representative influenza B strains tested, with higher potency and broader breadth of anti-influenza activity in vitro than the IgG subtype variant of itself, or other previously-reported influenza B bnAbs. Furthermore, C7G6-IgM conferred excellent cross-protection against distinct lineages of influenza B viruses in mice and ferrets, performing better than the anti-influenza drug oseltamivir, and showed an additive antiviral effect when administered in combination with oseltamivir. Mechanistically, C7G6-IgM potently inhibits infection with influenza B virus strains from different lineages by blocking viral entry. Conclusion: In summary, our study highlights the potential of IgM subtype antibodies in combatting pathogenic microbes. Moreover, C7G6-IgM is a promising candidate for the development of prophylactics or therapeutics against influenza B infection.-
dc.languageeng-
dc.publisherIvyspring International Publisher. The Journal's web site is located at http://www.thno.org/-
dc.relation.ispartofTheranostics-
dc.rightsTheranostics. Copyright © Ivyspring International Publisher.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectinfluenza B virus-
dc.subjecthemagglutinin-
dc.subjectreceptor binding site-
dc.subjectbroadly neutralizing antibodies-
dc.subjectIgM-
dc.titleAn IgM antibody targeting the receptor binding site of influenza B blocks viral infection with great breadth and potency-
dc.typeArticle-
dc.identifier.emailChen, H: hlchen@hku.hk-
dc.identifier.authorityChen, H=rp00383-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.7150/thno.28434-
dc.identifier.pmid30662563-
dc.identifier.pmcidPMC6332795-
dc.identifier.scopuseid_2-s2.0-85059504131-
dc.identifier.hkuros298558-
dc.identifier.volume9-
dc.identifier.issue1-
dc.identifier.spage210-
dc.identifier.epage231-
dc.publisher.placeAustralia-

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