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.