Multimerization of secretory IgA enhances antiviral activity by aggregating influenza A virus particles
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Le résumé fourni par la source
Secretory immunoglobulin A (sIgA), the first line of defense against mucosal epithelial infections, is a multimer. Although multimeric sIgA shows higher antiviral activity than monomeric IgA, the mechanism underlying this enhancement and the functional differences among IgA subclasses remain unclear. Here, we generated recombinant monomeric and multimeric IgA1 and IgA2m2 antibodies from clone F045-092, which targets the head domain of influenza A virus (IAV) hemagglutinin (HA) and inhibits viral entry, and compared their functional properties. Monomeric IgA1 inhibited viral entry but not viral release. Multimerization of IgA1 enhanced viral entry inhibition and conferred the additional function of inhibiting viral release. In contrast, monomeric IgA2m2 inhibited both viral entry and release and its multimerization enhanced these inhibitory effects. Importantly, treatment of IAV particles with multimeric sIgA or monomeric IgA2m2 induced viral aggregation via IgA-mediated tethering of neighboring virus particles, as visualized via cryo-electron tomography. Analysis of F(ab′)2 and Fab fragments from F045-092 IgA2m2 demonstrated that bivalency is essential for antibody-mediated viral aggregation (AVA) by monomeric IgA2m2, further supporting a direct tethering mechanism among virus particles. In conclusion, multimerization of the HA head-targeting IgA tends to enhance the inhibition of viral entry and release through AVA, contributing to its enhanced antiviral activity. Additionally, different IgA subclasses with identical variable regions can exhibit distinct properties in the monomeric form, and subclass switching may confer additional functions. Our findings contribute to the development of virus-aggregating antibodies as a new therapeutic approach that efficiently inhibits viral entry and release at the mucosal epithelium. Multimeric secretory IgA efficiently neutralizes influenza A virus by cross-linking viral particles, and distinct inhibitory effects on viral release are observed among different IgA subclasses.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Multimerization of secretory IgA enhances antiviral activity by aggregating influenza A virus particles
- Date Crossref
- 15/04/2026
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Kyoto University Laboratory of Ultrastructural Virology pays non établi dans la noticeUniversité ou école supérieure
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Max Planck Institute of Biochemistry pays non établi dans la noticeStructure de recherche
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Hokkaido University Institute for Vaccine Research and Development (HU-IVReD) pays non établi dans la noticeUniversité ou école supérieure
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National Institute of Infectious Diseases Department of Infectious Disease Pathology pays non établi dans la noticeOrganisme public
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Chiba University pays non établi dans la noticeUniversité ou école supérieure
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Graduate School of Biostudies Laboratory of Ultrastructural Virology pays non établi dans la noticeUniversité ou école supérieure
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Max Plank Institute of Biochemistry Department of Cell and Virus Structure pays non établi dans la noticeStructure de recherche
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Influenza Research Center pays non établi dans la noticeStructure de recherche
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Graduate School of Medicine Department of Infectious Disease Pathobiology pays non établi dans la noticeUniversité ou école supérieure
Laboratory of Ultrastructural Virology — Kyoto University, Max Planck Institute of Biochemistry et Institute for Vaccine Research and Development (HU-IVReD) — Hokkaido University, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.