TY - JOUR
T1 - Evaluation of Psn, HmuR and a modified LcrV protein delivered to mice by live attenuated Salmonella as a vaccine against bubonic and pneumonic Yersinia pestis challenge
AU - Branger, Christine G.
AU - Sun, Wei
AU - Torres-Escobar, Ascención
AU - Perry, Robert
AU - Roland, Kenneth L.
AU - Fetherston, Jacqueline
AU - Curtiss, Roy
N1 - Funding Information:
We thank S. Straley for providing pHT-V.J. Kilbourne is thanked for her expert assistance with animal experiments. This work was supported by National Institutes of Health grant 5R01 AI057885 .
PY - 2010/12/16
Y1 - 2010/12/16
N2 - We evaluated the ability of Yersinia pestis antigens HmuR, Psn and modified forms of LcrV delivered by live attenuated Salmonella strains to stimulate a protective immune response against subcutaneous or intranasal challenge with Y. pestis CO92. LcrV196 is a previously described truncated protein that includes aa 131-326 of LcrV and LcrV5214 has been modified to replace five key amino acids required for interaction with the TLR2 receptor. Psn is the outer membrane receptor for the siderophore, yersiniabactin, and the bacteriocin, pesticin. Mice immunized with Salmonella synthesizing Psn, LcrV196 or LcrV5214 developed serum IgG responses to the respective Yersinia antigen and were protected against pneumonic challenge with Y. pestis. Immunization with Salmonella synthesizing Psn or LcrV196 was sufficient to afford nearly full protection against bubonic challenge, while immunization with the strain synthesizing LcrV5214 was not protective. Immunization with Salmonella synthesizing HmuR, an outer membrane protein involved in heme acquisition in Y. pestis, was poorly immunogenic and did not elicit a protective response against either challenge route. These findings indicate that both Psn and LcrV196 delivered by Salmonella provide protection against both bubonic and pneumonic plague.
AB - We evaluated the ability of Yersinia pestis antigens HmuR, Psn and modified forms of LcrV delivered by live attenuated Salmonella strains to stimulate a protective immune response against subcutaneous or intranasal challenge with Y. pestis CO92. LcrV196 is a previously described truncated protein that includes aa 131-326 of LcrV and LcrV5214 has been modified to replace five key amino acids required for interaction with the TLR2 receptor. Psn is the outer membrane receptor for the siderophore, yersiniabactin, and the bacteriocin, pesticin. Mice immunized with Salmonella synthesizing Psn, LcrV196 or LcrV5214 developed serum IgG responses to the respective Yersinia antigen and were protected against pneumonic challenge with Y. pestis. Immunization with Salmonella synthesizing Psn or LcrV196 was sufficient to afford nearly full protection against bubonic challenge, while immunization with the strain synthesizing LcrV5214 was not protective. Immunization with Salmonella synthesizing HmuR, an outer membrane protein involved in heme acquisition in Y. pestis, was poorly immunogenic and did not elicit a protective response against either challenge route. These findings indicate that both Psn and LcrV196 delivered by Salmonella provide protection against both bubonic and pneumonic plague.
KW - LcrV
KW - Psn
KW - Recombinant attenuated Salmonella vaccine
KW - Yersinia pestis
UR - http://www.scopus.com/inward/record.url?scp=78649697669&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78649697669&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2010.10.033
DO - 10.1016/j.vaccine.2010.10.033
M3 - Article
C2 - 20979987
AN - SCOPUS:78649697669
SN - 0264-410X
VL - 29
SP - 274
EP - 282
JO - Vaccine
JF - Vaccine
IS - 2
ER -