Both
IgA and
IgG antibodies are known to play important roles in protection against influenza virus
infection. While
IgG is the major isotype induced systemically,
IgA is predominant in mucosal tissues, including the upper respiratory tract. Although
IgA antibodies are believed to have unique advantages in mucosal immunity, information on direct comparisons of the in vitro
antiviral activities of
IgA and
IgG antibodies recognizing the same
epitope is limited. In this study, we demonstrate differences in
antiviral activities between these isotypes using monoclonal
IgA and
IgG antibodies obtained from hybridomas of the same origin.
Polymeric IgA-producing hybridoma cells were successfully subcloned from those originally producing
monoclonal antibody S139/1, a hemaggulutinin (HA)-specific
IgG that was generated against an influenza A virus strain of the H3 subtype but had cross-neutralizing activities against the H1, H2, H13, and
H16 subtypes. These monoclonal S139/1
IgA and
IgG antibodies were assumed to recognize the same
epitope and thus used to compare their
antiviral activities. We found that both S139/1
IgA and
IgG antibodies strongly bound to the homologous H3 virus in an
enzyme-linked
immunosorbent assay, and there were no significant differences in their hemagglutination-inhibiting and neutralizing activities against the H3 virus. In contrast, S139/1
IgA showed remarkably higher cross-binding to and
antiviral activities against H1, H2, and H13 viruses than S139/1
IgG. It was also noted that S139/1
IgA, but not
IgG, drastically suppressed the extracellular release of the viruses from infected cells. Electron microscopy revealed that S139/1
IgA deposited newly produced viral particles on the cell surface, most likely by tethering the particles. These results suggest that anti-HA
IgA has greater potential to prevent influenza A virus
infection than
IgG antibodies, likely due to increased avidity conferred by its multivalency, and that this advantage may be particularly important for heterosubtypic immunity.