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 expre ssed in two cell lineages. The heavy and light chains as well as the J chai n are produced in plasma cells, whereas the secretory component (SC) is ass ociated to the immunoglobulin complex during transcytosis across the epithe lial layer. S-IgA antibodies represent the predominant immunoglobulin class in external secretions, and the best defined entity providing specific imm une protection for mucosal surfaces by blocking attachment of bacteria and viruses, S-IgA constitutes greater than 80% of all antibodies produced in m ucosa-associated lymphoid tissues in humans. The existence of a common muco sal immune system permits immunization on one mucosal surface to induce sec retion of antigen-specific S-IgA at distant sites. In addition, S-IgA antib odies not only function in external secretions, but also exert their antimi crobial properties within the epithelial cell during transport across the e pithelium. Passive mucosal delivery of monoclonal IgA molecules neutralizes pathogens responsible for gastrointestinal and respiratory infections. Muc osal and systemic immunity can be achieved by orally administered recombina nt S-IgA molecules carrying a protective bacterial epitope within the SC po lypeptide primary sequence.