Gamma‐irradiated pCD1‐ Yersinia pestis vaccine is protective: an anti‐LcrV response is not necessary to protect against the plague

Abstract

Yersinia pestis is the cause of plague and a potential weapon for bioterrorism. We have reported that immunization with lethally‐irradiated Y. pestis Kim5 is protective against subsequent i.v. challenges with the plague. We report here that pCD1‐Y. pestis, lacking the TTSS, provides protection comparable to wild‐type Y. pestis. Both strains provided protection against >107 CFU challenge of wildtype Y. pestis, compared to sham‐vaccinated mice that displayed an LD50 of 1.4X104 CFUs. This finding suggests that LcrV, located on pCD1 and previously shown to provide significant protection, was not essential for protection. A limited number of antibody specificities were generated by the irradiated wildtype or pCD1‐ Y. pestis, 6–8 unique specificities as determined by immunoblotting. The majority of these immunodominant specificities were shown to reside on the outer surface of the bacteria. Although this work has focused on humoral responses, T cell immunodominant epitopes can be rapidly identified with the irradiated vaccine as well. Lethal gamma‐irradiation provides a novel approach for the rapid production of vaccines that have remained elusive. Using a whole cell vaccine also allows for the rapid assessment of the immunodominant “footprint” to the majority of antigens present, aiding in the identification of putative sub‐unit vaccine candidates.