A Recombinant Attenuated Yersinia pseudotuberculosis Vaccine Delivering a Y. pestis YopE_Nt138-LcrV Fusion Elicits Broad Protection against Plague and Yersiniosis in Mice.

ABSTRACT: In this study, a novel recombinant attenuated Yersinia pseudotuberculosis PB1+ strain (?10069) engineered with ?yopK ?yopJ ?asd triple mutations was used to deliver a Y. pestis fusion protein, YopE amino acid 1 to 138-LcrV (YopE_Nt138-LcrV), to Swiss Webster mice as a protective antigen against infections by yersiniae. ?10069 bacteria harboring the pYA5199 plasmid constitutively synthesized the YopE_Nt138-LcrV fusion protein and secreted it via the type 3 secretion system (T3SS) at 37°C under calcium-deprived conditions. The attenuated strain ?10069(pYA5199) was manifested by the establishment of controlled infection in different tissues without developing conspicuous signs of disease in histopathological analysis of microtome sections. A single-dose oral immunization of ?10069(pYA5199) induced strong serum antibody titers (log₁₀ mean value, 4.2), secretory IgA in bronchoalveolar lavage (BAL) fluid from immunized mice, and Yersinia-specific CD4⁺ and CD8⁺ T cells producing high levels of tumor necrosis factor alpha (TNF-?), gamma interferon (IFN-?), and interleukin 2 (IL-2), as well as IL-17, in both lungs and spleens of immunized mice, conferring comprehensive Th1- and Th2-mediated immune responses and protection against bubonic and pneumonic plague challenges, with 80% and 90% survival, respectively. Mice immunized with ?10069(pYA5199) also exhibited complete protection against lethal oral infections by Yersinia enterocolitica WA and Y. pseudotuberculosis PB1+. These findings indicated that ?10069(pYA5199) as an oral vaccine induces protective immunity to prevent bubonic and pneumonic plague, as well as yersiniosis, in mice and would be a promising oral vaccine candidate for protection against plague and yersiniosis for human and veterinary applications.

SUBMITTER: Singh AK 

PROVIDER: S-EPMC6759313 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature