16 - Oral Vaccines for Shigella

Abstract

This chapter discusses the pathogenesis and molecular biology of Shigella infections that result in the development of Bacillary Dysentery. In 1964, it was proposed that the key step of the pathogenesis of bacillary dysentery is the apical infection of the colonic epithelial cells by virulent Shigellae. In vitro, undifferentiated epithelial cells were found to be susceptible to Shigella infection, thus providing a relatively simple system to study the details of Shigella–host cell interactions. Bacillary dysentery is an acute enterocolitis. The symptoms include fever and diarrhea that may progress to dysentery, i.e., intestinal cramps and tenesmus, with frequent passage of small volume, mucoid, often bloody stool. Shigella genus contains four species, namely, S. dysenteriae, S. flexneri, S. boydii, and S. sonnei, each divided into 12, 13, 18, and 1 serotypes, respectively. The chapter discusses a model explaining the mechanism through which this pathogen causes infection. The immunity after natural or experimental infections, as well as after vaccines, is serotype specific. The severity of shigellosis in immunodeficient patients indicates the active involvement of cell- mediated effector mechanisms in fighting Shigellae. The chapter also discusses the vaccine development that is affected by the understanding of the pathogenesis and the immune defense mechanisms against shigellosis. The main goal of all Shigella vaccine is to deliver as much “protective” antigenic stimulus as possible to trigger the strongest tolerable mucosal immune response in the host. However, there are limitations associated with the development of a safe vaccine against Bacillary Dysentery—that is, uncertainty on the kind of defense mechanism to be stimulated and the process through which memory mechanisms are to be regulated. The chapter concludes by providing the best prophylactic measure to prevent the Shigellae from invading the mucosal lining of the intestine, that is, to limit the intracellular multiplication and spread of the bacteria in the tissues