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Potential Role of Nonneutralizing IgA Antibodies in Cross-Protective Immunity against Influenza A Viruses of Multiple Hemagglutinin Subtypes

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Title: Potential Role of Nonneutralizing IgA Antibodies in Cross-Protective Immunity against Influenza A Viruses of Multiple Hemagglutinin Subtypes
Authors: Okuya, Kosuke Browse this author
Yoshida, Reiko Browse this author
Manzoor, Rashid Browse this author
Saito, Shinji Browse this author
Suzuki, Tadaki Browse this author
Sasaki, Michihito Browse this author
Saito, Takeshi Browse this author
Kida, Yurie Browse this author
Mori-Kajihara, Akina Browse this author
Kondoh, Tatsunari Browse this author
Sato, Masahiro Browse this author
Kajihara, Masahiro Browse this author
Miyamoto, Hiroko Browse this author
Ichii, Osamu Browse this author
Higashi, Hideaki Browse this author
Takada, Ayato Browse this author →KAKEN DB
Keywords: IgA
broadly cross-reactive
cross-protective immunity
influenza A virus
Issue Date: Jun-2020
Publisher: American Society for Microbiology
Journal Title: Journal of Virology
Volume: 94
Issue: 12
Start Page: e00408-20
Publisher DOI: 10.1128/JVI.00408-20
Abstract: IgA antibodies on mucosal surfaces are known to play an important role in protection from influenza A virus (IAV) infection and are believed to be more potent than IgG for cross-protective immunity against IAVs of multiple hemagglutinin (HA) subtypes. However, in general, neutralizing antibodies specific to HA are principally HA subtype specific. Here, we focus on nonneutralizing but broadly cross-reactive HA-specific IgA antibodies. Recombinant IgG, monomeric IgA (mIgA), and polymeric secretory IgA (pSIgA) antibodies were generated based on the sequence of a mouse anti-HA monoclonal antibody (MAb) 5A5 that had no neutralizing activity but showed broad binding capacity to multiple HA subtypes. While confirming that there was no neutralizing activity of the recombinant MAbs against IAV strains A/Puerto Rico/8/1934 (H1N1), A/Adachi/2/1957 (H2N2), A/Hong Kong/483/1997 (H5N1), A/shearwater/South Australia/1/1972 (H6N5), A/duck/England/1/1956 (H11N6), and A/duck/Alberta/60/1976 (H12N5), we found that pSIgA, but not mIgA and IgG, significantly reduced budding and release of most of the viruses from infected cells. Electron microscopy demonstrated that pSIgA deposited newly produced virus particles on the surfaces of infected cells, most likely due to tethering of virus particles. Furthermore, we found that pSIgA showed significantly higher activity to reduce plaque sizes of the viruses than IgG and mIgA. These results suggest that nonneutralizing pSIgA reactive to multiple HA subtypes may play a role in intersubtype cross-protective immunity against IAVs. IMPORTANCE Mucosal immunity represented by pSIgA plays important roles in protection from IAV infection. Furthermore, IAV HA-specific pSIgA antibodies are thought to contribute to cross-protective immunity against multiple IAV subtypes. However, the mechanisms by which pSIgA exerts such versatile antiviral activity are not fully understood. In this study, we generated broadly cross-reactive recombinant IgG and pSIgA having the same antigen-recognition site and compared their antiviral activities in vitro. These recombinant antibodies did not show "classical" neutralizing activity, whereas pSIgA, but not IgG, significantly inhibited the production of progeny virus particles from infected cells. Plaque formation was also significantly reduced by pSIgA, but not IgG. These effects were seen in infection with lAVs of several different HA subtypes. Based on our findings, we propose an antibody-mediated host defense mechanism by which mucosal immunity may contribute to broad cross-protection from lAVs of multiple HA subtypes, including viruses with pandemic potential.
Rights: Copyright © American Society for Microbiology, [Journal of Virology, 94(12), 2020, e00408-20 , 10.1128/JVI.00408-20]
Type: article
Appears in Collections:人獣共通感染症リサーチセンター (Research Center for Zoonosis Control) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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