An influenza HA stalk reactive polymeric IgA antibody exhibits anti-viral function regulated by binary interaction between HA and the antibody

• Published in: PloS one Vol. 16; no. 1; p. e0245244
• Main Authors: Sano, Kaori, Saito, Shinji, Suzuki, Tadaki, Kotani, Osamu, Ainai, Akira, van Riet, Elly, Tabata, Koshiro, Saito, Kumpei, Takahashi, Yoshimasa, Yokoyama, Masaru, Sato, Hironori, Maruno, Takahiro, Usami, Kaede, Uchiyama, Susumu, Ogawa-Goto, Kiyoko, Hasegawa, Hideki
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 07.01.2021; Public Library of Science (PLoS)
• Subjects: Animals; Antibodies; Antibodies, Viral - chemistry; Antibodies, Viral - immunology; Antibody Affinity; Antiviral agents; Antiviral drugs; Binding sites; Binding Sites, Antibody; Biology and Life Sciences; Biotechnology; Cells, Cultured; Cloning; Dogs; Engineering schools; Fab; Female; Genomics; Glycan; Health aspects; HEK293 Cells; Hemagglutination inhibition; Hemagglutinins; Hemagglutinins - chemistry; Hemagglutinins - immunology; Humans; Immunogenicity, Vaccine; Immunoglobulin A; Immunoglobulin A - chemistry; Immunoglobulin A - immunology; Immunoglobulin G; Infections; Infectious diseases; Influenza; Influenza A Virus, H5N1 Subtype - immunology; Influenza Vaccines - immunology; Influenza, Human - prevention & control; Madin Darby Canine Kidney Cells; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Mucosa; Neutralization; Pathogens; Pathology; Physical Sciences; Polymerization; Polymers; Prevention; Properties (attributes); Research and Analysis Methods; Testing; Vaccines; Viruses; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0245244

IgA antibodies, which are secreted onto the mucosal surface as secretory IgA antibodies (SIgAs), play an important role in preventing influenza virus infection. A recent study reported that anti-hemagglutinin (HA) head-targeting antibodies increase anti-viral functions such as hemagglutination inhibition (HI) and virus neutralization (NT), in addition to HA binding activity (reactivity) via IgA polymerization. However, the functional properties of anti-viral IgA antibodies with mechanisms of action distinct from those of anti-HA head-targeting antibodies remain elusive. Here, we characterized the functional properties of IgG, monomeric IgA, and polymeric IgA anti-HA stalk-binding clones F11 and FI6, and B12 (a low affinity anti-HA stalk clone), as well as Fab-deficient (ΔFab) IgA antibodies. We found that IgA polymerization impacts the functional properties of anti-HA stalk antibodies. Unlike anti-HA head antibodies, the anti-viral functions of anti-HA stalk antibodies were not simply enhanced by IgA polymerization. The data suggest that two modes of binding (Fab paratope-mediated binding to the HA stalk, and IgA Fc glycan-mediated binding to the HA receptor binding site (RBS)) occur during interaction between anti-stalk HA IgA antibodies and HA. In situations where Fab paratope-mediated binding to the HA stalk exceeded IgA Fc glycan-mediated binding to HA RBS, IgA polymerization increased anti-viral functions. By contrast, when IgA Fc glycan-mediated binding to the HA RBS was dominant, anti-viral activity will fall upon IgA polymerization. In summary, the results suggest that coordination between these two independent binding modules determines whether IgA polymerization has a negative or positive effect on the anti-viral functions of anti-HA stalk IgA antibodies.