The mucosal immune system for secretory IgA responses and mucosal vaccine development

Abstract

Immunoglobulin A (IgA) is the body's predominant antibody isotype, and the bulk of the body's IgA-producing cells reside in various mucosal and exocrine tissues. Production of IgA at mucosal surfaces is strictly regulated through coordinated communication among mucosal B and T cells, mucosal dendritic cells (DCs), and epithelial cells. Although organized lymphoid tissues such as Peyer's patches (PP) have long been recognized as key sources of IgA plasma cells at mucosal surfaces, IgA-mediated mucosal immune response is maintained even in PP-null conditions. Mucosal DCs likely are specialized to provide help to B cells to promote IgA-producing plasma cells. Intriguingly, induction of the proliferation of microbiota-specific IgA+ B cells is independent of T helper activity but may depend on lamina propria DCs expressing iNOS, CX3CR1, and TLR5. In the quest to develop an oral vaccine to boost mucosal immunity, rice was genetically engineered to express the B subunit of cholera toxin (CT-B). The recombinant CT-B that accumulates in the protein bodies of rice is resistant to the harsh gastrointestinal environment, and immunization of mice with the vaccine provoked a protective mucosal IgA response against CT. Furthermore, the vaccine is stable and maintains immunogenicity at room temperature for at least 24 months. Because they are easy to administer and requires neither refrigeration nor needles, rice-based mucosal vaccines are highly practical for global immunization against infectious diseases. Rec.8/13/2008, Acc.2/6/2009, pp40-47