Construction and evaluation of a virG thyA double mutant of Shigella flexneri 2a as a candidate live-attenuated oral vaccine.

A virG thyA double mutant of Shigella flexneri 2a was constructed as a candidate live-attenuated oral vaccine. In the keratoconjunctivitis model it did not provoke any adverse reaction by itself on guinea pigs' eyes and completely protected them from provoking keratoconjunctivitis. When (2.7-4.8) x 10(10) of the vaccine was inoculated intragastrically after 1 day fasting in cynomolgus monkeys three times at weekly intervals, a watery stool was observed at 40% as a side-effect. Upon intragastric challenge after 1 day fasting with 7.5 x 10(9) of the virulent strain four weeks after the last vaccination, a statistically significant difference was obtained in the mortality rate but not in the morbidity rate between the vaccine and the control group, although the clinical findings were less severe in the vaccine group than in the control group. These results together with the histopathological and immunological findings indicate that the vaccine deserve further detailed studies.