The Experimental Basis for Oral Immunisation Against Cholera

Abstract

For nearly a century cholera immunisation has been given parenterally, with very limited success. Experimental vaccines have varied in antigenic composition, but not in route of administration. Recent studies on immunologic defence of the gut emphasise the role of intraluminal (secretory) antibody in protection against non-invasive pathogens, such as V. cholerae, and permitted detailed comparison of the effectiveness of parenteral or local (oral) immunisation in stimulating protective responses.

Parenteral immunisation may provide brief protection by stimulating high, but transient, levels of serum IgG antibody, which enters the gut passively and inefficiently. Under some conditions, parenteral immunisation may also stimulate the mucosal IgA immune system, but this effect is followed by long-lasting suppression of the mucosal IgA response and cannot be repeated. In contrast, the enteric mucosal immune system appears designed for efficient response to mucosal antigens and protection of mucosal surfaces. This design includes specialised mechanisms for sampling of mucosal antigens, cellular traffic patterns which disseminate immunologic memory to distant mucosae but focus the specific antibody response at the site of antigen exposure, and the production of secretory IgA antibody which is efficiently secreted to the mucosal surface. Some features of antigens which favour mucosal immunogenicity have been identified and long-lasting memory in this system has been observed. Oral immunisation with killed or living bacterial antigens has been shown to evoke relatively long-lasting protection against mucosal infection.

Present evidence strongly favours oral immunisation with appropriately selected antigens as the best approach to immunoprophylaxis of cholera and related enteric infections.