Multimerization of secretory IgA enhances antiviral activity by aggregating influenza A virus particles

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.