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.

To evaluate whether cellular immunity can protect against plague, we vaccinated B cell-deficient mice with live attenuated Y. pestis.  Although B cell-deficient mice cannot generate humoral immunity, vaccination protected these animals against pneumonic plague.  Depleting T cells from the vaccinated mice abrogated the protection.  Transferring vaccine-primed T cells to naïve mice conferred protection.  We conclude that cellular immunity mediated by vaccine-primed T cells can protect against plague.

Current efforts are aimed at identifying the Y. pestis antigens that elicit protective cellular responses and defining the mechanisms of protection.  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.