Potentials of Shigella flexneri Y strain TSF21 as a candidate vaccine against shigellosis: safety, immunogenicity and protective efficacy in Bonnet monkeys

Abstract

A thymine-requiring and temperature-sensitive mutant of Shigella flexneri Y was tested in Bonnet monkeys for safety, immunogenicity and protective efficacy. A dose of 10(11) cells when fed orally mimicked natural infection in having invaded epithelial cells, but was otherwise clinically non-reactogenic. Animals immunized with two oral doses, each dose consisting of 1 x 10(11) mutant bacteria, were fully protected when challenged, with respect to the lack of any clinical symptoms or detectable histological abnormalities in the intestinal mucosa. Unimmunized animals when similarly challenged developed frank dysentery and the intestinal mucosa showed severe histological abnormalities. Titres of serum antibodies increased by about 11-fold of the base level in animals immunized with a dose of 10(11) cells, but not with lower doses. The challenge bacteria appeared to be phagocytised by macrophages. In some monkeys of a particular group, congestive patches were seen in the stomach, but not in any other part of the gut, after the animals were fed with the virulent parent strain. The lesions were relatively severe in the immunized groups of animals.