B cell responses to influenza infection and vaccination.

Although vaccines against influenza are widely available, control of the disease remains elusive. In part, this is due to the inability of current vaccines to induce durable, broadly protective immune responses. Prevention of influenza depends primarily on effective antibody responses that block virus entry. Following infection, high-affinity IgA antibodies are generated in the respiratory tract that lead to immune exclusion, while IgG prevents systemic spread. These are effective and long-lasting but also exert immune pressure. Mutation of the antigenic determinants of influenza therefore rapidly leads to emergence of novel variants that evade previously generated protective responses. Not only do vaccines suffer from this strain-specific limitation, but also they are suboptimal in their ability to induce durable immunity. However, recent evidence has demonstrated the possibility of inducing broadly cross-reactive antibody responses. Further understanding of the ways in which high-titer, long-lived antibody responses directed against such cross-reactive epitopes can be induced would lead to the development of novel vaccines that may remove the requirement for recurrent vaccination.