Prospects for human mucosal vaccines

The selective induction of antibodies in external secretions and mucosal T cell-mediated immunity are desirable for the prevention of various systemic as well as predominantly mucosa-restricted infections. An enormous surface area of mucosal membranes is protected primarily by antibodies that belong, in many species, to the IgA isotype. Such antibodies are produced locally by large numbers of IgA-containing plasma cells distributed in subepithelial spaces of mucosal membranes and in the stroma of secretory glands. In humans and in some animal species, plasma-derived IgA antibodies do not enter external secretions in significant quantities and systemically administered preformed IgA antibodies would be of little use for passive immunization. Systemic administration of microbial antigens may boost an effective S-IgA immune response only in a situation whereby an immunized individual had previously encountered the same antigen by the mucosal route. Immunization routes that involve ingestion or possibly inhalation of antigens lead to the induction of not only local but also generalized immune responses, manifested by the parallel appearance of S-IgA antibodies to ingested or inhaled antigens in secretions of glands distant from the site of immunization. Convincing evidence is available that antigen-sensitized and IgA-committed precursors of plasma cells and T cells from IgA inductive sites (e.g., BALT, GALT, and tonsils) are disseminated to the gut, other mucosa-associated tissues, and exocrine glands. However, due to the limited absorption of desired antigens from the gut lumen of orally immunized individuals, repeated large doses of antigens are required for an effective S-IgA response. Novel antigen delivery systems for the stimulation of such responses has been briefly reviewed here. These, of course, include genetically engineered bacteria and viruses, CT/CFB, liposomes and microspheres. Live attenuated or genetically manipulated bacteria expressing other microbial antigens have been used for selective colonization of GALT. Unique antigen packaging and the use of adjuvants suitable for oral administration hold promise for an efficient antigen delivery to critical tissues in the intestine and deserve extensive exploration. The oral immunization route appears to have many advantages over systemic immunization; however, one must consider alternate IgA inductive sites and compartmentalization within the Common Mucosal Immune System. In addition to providing immunity on mucosal surfaces, which are the most common sites of entry of infectious agents, the mucosal routes of administration are more acceptable and do not require stringent criteria applicable for injectable vaccines, storage problems may be simplified, and large populations of individuals can be immunized simultaneously without the assistance of highly trained health personnel.