15 - Human Mucosal Vaccines for Salmonella typhi Infections

Abstract

This chapter discusses the human mucosal vaccines for Salmonella typhi (S. typhi) infections. In less-developed countries, people that do not receive treated water supplies and sanitation to remove human waste, typhoid fever is often endemic. It typically is the most enteric public health problem, especially in the case of school-age children. The chapter discusses the pathogenesis of the of wild-type S. typhi infection, which is important for designing strategies to attenuate typhoid bacilli in a rational manner so that they can be used as live oral vaccines. S . typhi are highly invasive, human host-adapted bacteria that rapidly and efficiently pass through the intestinal mucosa of man to eventually reach the reticuloen-dothelial system where, after an 8- to 14-day incubation period, they precipitate a systemic illness . The inoculum size and the type of vehicle in which it is ingested greatly influence the attack rate for typhoid fever and also affect the incubation period. The chapter also details the mechanism through which S. typhi attacks and causes infection. The chapter also discusses the vaccination for S. typhi that includes parenteral and live vaccines development and treatment. Studies on typhoid patients and volunteers orally immunized with attenuated S. typhi strains have resulted in a mechanism of immune response against enteric pathogens that appears to be a form of antibody dependent cellular cytotoxicity (ADCC) involving peripheral blood mononuclear cells and immune serum. The application of recombinant DNA technology has allowed the rational attenuation of S. typhi to yield strains to serve as candidate live oral vaccines to prevent typhoid fever.