IgA antibodies contribute to protection against influenza virus infection

IgA antibody, whose production exceeds that of all other immunoglobulin classes combined, is the major immunoglobulin isotype in humans. In addition, IgA antibody, which is secreted onto the mucosal surface as a secretory IgA antibody (SIgA), plays an important role as a first line of defense by inactivating pathogens such as influenza viruses, and is a key molecule that underpins the action of intranasal influenza vaccines. Therefore, understanding how SIgA works is important if we are to accelerate development of the intranasal influenza vaccines. A recent report shows that the polymerization status of SIgA defines their functionality in the human upper respiratory mucosa. Higher order polymerization of SIgA such as a tetrameric form leads to a marked increase in neutralizing activity against influenza viruses. Moreover, we developed a method for generating tetrameric SIgA monoclonal antibodies, and then compared the anti-viral function of the tetrameric SIgA with that of monomeric IgG or IgA. The analysis revealed that tetramerization of SIgA improved target breadth, but not peak potency of antiviral functions. This phenomenon presumably represents one of the mechanisms by which mucosal SIgAs induced by intranasal influenza vaccines show potential antiviral activities against broad range of influenza viruses. These results broaden our knowledge about the fundamental role of SIgA in influenza protection.