Oral administration of a recombinant attenuated Yersinia pseudotuberculosis strain elicits protective immunity against plague.

ABSTRACT: A Yersinia pseudotuberculosis PB1+ (Yptb PB1+) mutant strain combined with chromosome insertion of the caf1R-caf1A-caf1M-caf1 operon and deletions of yopJ and yopK, ?10068 [pYV-?2 (?yopJ315 ?yopK108) ?lacZ044::caf1R-caf1M-caf1A-caf1] was constructed. Results indicated that gene insertion and deletion did not affect the growth rate of ?10068 compared to wild-type Yptb cultured at 26 °C. In addition, the F1 antigen in ?10068 was synthesized and secreted on the surface of bacteria at 37 °C (mammalian body temperature), not at ambient culture temperature (26 °C). Immunization with ?10068 primed antibody responses and specific T-cell responses to F1 and YpL (Y. pestis whole cell lysate). Oral immunization with a single dose of ?10068 provided 70% protection against a subcutaneous (s.c.) challenge with ? 2.6 × 10(5) LD50 of Y. pestis KIM6+ (pCD1Ap) (KIM6+Ap) and 90% protection against an intranasal (i.n.) challenge with ? 500 LD50 of KIM6+Ap in mice. Our results suggest that ?10068 can be used as an effective precursor to make a safe vaccine to prevent plague in humans and to eliminate plague circulation among humans and animals.

SUBMITTER: Sun W 

PROVIDER: S-EPMC4679553 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature