Oral inoculation with Type III secretion mutants of Yersinia pseudotuberculosis provides protection from oral, intraperitoneal, or intranasal challenge with virulent Yersinia.

The enteric pathogen Yersinia pseudotuberculosis (Yptb) causes gastroenteritis, mesenteric lymphadenitis, and systemic infections in humans, livestock, and wild animals. Yptb Type III secretion system (pTTSS) mutants efficiently colonize lymphoid tissues, but not the gastrointestinal tract, spleen, or liver. Here, we show that a single oral inoculation of pTTSS mutants prevents morbidity in almost 100% of mice challenged intragastrically with virulent Yptb. In addition, a single oral inoculation of a pTTSS mutant protected 50% of mice challenged intraperitoneally or intranasally with virulent Yptb. In addition, the intranasally challenged mice that succumbed to infection lived significantly longer than non-immunized mice. Thus, pTTSS mutants can function as live attenuated vaccine when delivered orally. Potential uses for these attenuated strains include use as a livestock vaccine, a rodent plague control reagent in endemic areas around the world, and a vector for delivery of other antigens to the mesenteric lymph nodes.