Secretory immunoglobulin A: from mucosal protection to vaccine development

Immune responses taking place in mucosal tissues are typified by secretory immunoglobulin A (S-IgA) molecules, which are assembled from proteins expressed in two cell lineages. The heavy and light chains as well as the J chain are produced in plasma cells, whereas the secretory component (SC) is associated to the immunoglobulin complex during transcytosis across the epithelial layer. S-IgA antibodies represent the predominant immunoglobulin class in external secretions, and the best defined entity providing specific immune protection for mucosal surfaces by blocking attachment of bacteria and viruses. S-IgA constitutes greater than 80% of all antibodies produced in mucosa-associated lymphoid tissues in humans. The existence of a common mucosal immune system permits immunization on one mucosal surface to induce secretion of antigen-specific S-IgA at distant sites. In addition, S-IgA antibodies not only function in external secretions, but also exert their antimicrobial properties within the epithelial cell during transport across the epithelium. Passive mucosal delivery of monoclonal IgA molecules neutralizes pathogens responsible for gastrointestinal and respiratory infections. Mucosal and systemic immunity can be achieved by orally administered recombinant S-IgA molecules carrying a protective bacterial epitope within the SC polypeptide primary sequence.