Evaluation of YadC protein delivered by live attenuatedSalmonellaas a vaccine against plague

Abstract

Yersinia pestis YadB and YadC are two new outer membrane proteins related with its pathogenicity. Here, codon optimized yadC, yadC810 (aa 32-551) or yadBC antigen genes delivered by live attenuated Salmonella strains are evaluated in mice for induction of protective immune responses against Y. pestis CO92 through subcutaneous (s.c.) or intranasal (i.n.) challenge. Our findings indicate that mice immunized with Salmonella synthesizing YadC, YadC810 or YadBC develop significant serum IgG responses to purified recombinant YadC protein. For s.c. challenge (~230 LD50 of Y. pestis CO92), mice immunized with Salmonella synthesizing YadC or YadC810 are afforded 50% protection but no protection by immunization with the Salmonella strain synthesizing YadBC. None of these antigens provided protection against i.n. challenge (~31 LD50 of Y. pestis CO92). In addition, s.c. immunization with purified YadC810 protein emulsified with Alum adjuvant does not elicit a protective response against Y. pestis administered by either challenge route.

Plague Vaccines: Status and Future

“…But immunization with the GST-YadC 137–409 protein, which fused YadC aa 137 to 409 to C terminal of glutathione S-transferase (GST), provided partial protection against F1 − Y. pestis challenge in mice and was found to stimulate mixed Th1/Th2 responses [51]. However, Sun et al showed that YadC810 protein immunization could not provide any protection against subcutaneous and intranasal challenge of virulent Y. pestis CO92 [52]. The explanations for this contrary result: 1) the higher challenge dose we used; 2) the YadC protein (aa 32–551) used for immunization in our studies was different with the YadC protein (aa 137–422) used by Murphy et al [51].…”

LcrV Delivered via Type III Secretion System of Live Attenuated Yersinia pseudotuberculosis Enhances Immunogenicity against Pneumonic Plague

“…With the exception of two additional plasmids (pPCP1 and pMT1) carried by Y. pestis, the two species share Ͼ95% genetic identity and a common virulence plasmid with a conserved colinear backbone (30). BLAST analysis of several major Y. pestis antigens showed that LcrV shares 96% amino acid identity between the two species and that Psn and YadC, two additional antigens shown to be protective against Y. pestis challenge (31)(32)(33), share 100% homology (34) and Ͼ97% homology (35), respectively. Furthermore, Y. pseudotuberculosis has a much lower number of insertion sequence (IS) copies than Y. pestis and so is genetically much more stable than the latter (30).…”

Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague

“…In addition to LcrV and F1, six other Y. pestis antigens individually, namely, Psn [12], HmuR [12], PsaA (pH 6 antigen) [40], YadC [41], Pla, and YopE (unpublished data) have been vectored by Salmonella in our research studies. However, only immunization with RASVs delivering Psn [12] or YadC afforded partial protection against Y. pestis challenge.…”

“…Recent work in our group showed that immunization with a mixture of the two RASVs, one delivering a carboxyl-terminal fragment of alpha toxin of Clostridium perfringens and the other a GST-NetB fusion protein induced protective immunity against C. perfringens in broiler chicks [42]. A similar approach could be applied for a mixture of two RASVs, one delivering LcrV, F1 and Psn antigens and the other another Y. pestis protective antigen, such as YopD [43], YscF [44], Ail [45] or YadC [41] to induce an optimal protective immune response.…”