This project focusses on enteric diseases caused by Shigella spp. (shigellosis) remain a serious and frequent cause of morbidity and mortality throughout the developing world especially in infants and children. Treatment of shigellosis has become difficult because most strains of Shigella are resistant to commonly used antibiotics. Shigellosis is the major cause of dysentery in infants and children with its serious complications: death or decreased growth and weight loss. In addition, shigellosis occurs in healthy individuals under conditions of crowding, such as in armed forces recruits, or in institutions caring for debilitated patients. Despite a century of study after its discovery, there are no licensed vaccines for prevention of shigellosis. This deficiency is due to our ignorance of what is/are the host protective immune moiety(ies) and a lack of a valid animal model for shigellosis. We have hypothesized that serum IgG antibodies to the O-specific polysaccharide of Shigella will confer protective immunity to shigellosis. The LPS of Shigella has been isolated and detoxified by acid hydrolysis. The detoxified LPS has been bound to several carrier proteins and Phase 1 and Phase 2 clinical studies have shown these investigational vaccines to be safe and immunogenic in adults. The level of conjugate vaccine antibodies is equal or higher than those in patients following shigellosis. In addition, the repeating unit of the O-specific polysaccharide of Shigella dysenteriae type 1 (Shiga) has been synthesized and the immunodominant epitope has been identified. This work is still in progress.
