The gram-negative bacterium Yersinia pestis causes plague, one of the world’s most deadly infectious diseases. There is significant concern that terrorists may aerosolize Y. pestis deliberately, thereby causing outbreaks of pneumonic plague. To date, pneumonic plague vaccine efforts have focused largely on antibody-based humoral protection. Despite success in mouse models, recent primate studies suggest that antibodies may not suffice to protect humans. Specifically, the US Army found that vaccine-primed humoral immunity fails to protect African green monkeys from aerosolized Y. pestis. We hypothesize that vaccines priming both humoral and cellular immunity will confer superior protection.
We have demonstrated that cellular immunity mediated by vaccine-primed T cells can protect against plague. We also identified a dominant antigen recognized by Y. pestis-specific CD8 T cells. Immunizing mice with this single CD8 T cell epitope suffices to confer significant protection against lethal pulmonary Y. pestis challenge. Moreover, we found that CD8 T cells combat Y. pestis via mechanisms that are critically dependent on cytokines IFNgamma and TNFalpha, but not cytotoxicity. Current efforts are aimed at extending our research to the fully virulent strain of Y. pestis, a CDC category A Select Agent. In addition, we are working to understand how Y. pestis thwarts our natural immune defense systems. These efforts should aid the development of vaccines and therapeutics for Y. pestis and other bacterial pathogens that infect the lung.