Strategies for the development of vaccines for typhoid fever, shigellosis, and cholera.

Abstract

Enteric fevers and diarrheal diseases are major causes of morbidity and mortality throughout the developing world.1 Traditional approaches to the development of vaccines for bacterial diseases include the parenteral injection of purified components or killed organisms.2 These methods require technologically advanced preparation and are relatively expensive despite their proven benefits. Live oral vaccine strains have several advantages over parenteral vaccines: low cost, ease of administration, and simple preparation.The development of live vaccines has been limited by lack of understanding of the pathogenesis of disease on a molecular level. Candidate live vaccine strains require nonrevertable genetic alterations that affect the virulence of the organism, but not its induction of an immune response. Work defining the mechanisms of toxigenesis of Vibrio cholerae has made it possible to create live vaccine strains based on deletion of the toxin genes.3,4 We will discuss below recent studies that have begun to define the molecular basis of Salmonella typhimurium macrophage survival and virulence. This may lead to the development of a live oral Salmonella typhi vaccine that can be used as a carrier for heterologous antigens. This approach has the advantage that immunity to multiple diseases could be generated with a single vaccine strain. Attenuated Salmonella typhi would deliver heterologous antigens directly to the immune effector cell, the macrophage, and generate cell‐mediated as well as humoral immune response.5