Cell-Mediated Defense Against Yersinia pestis Infection

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Yersinia pestis (Yp) - one of the world’s most deadly human pathogens - is the gram-negative bacterium that causes pneumonic plague. Virulent antibiotic-resistant Yp strains exist and Cold War scientists devised means to effectively aerosolize Yp. These facts raise grave concern that Yp will be exploited as a bioweapon. To counter that possibility, it is essential that we develop a safe and effective pneumonic plague vaccine. Recent studies suggest that the leading vaccine candidate, which primarily stimulates antibody-mediated humoral immunity, may not suffice. T cell-dependent cellular immunity comprises a second means by which vaccines prime long-lived protection against virulent bacterial pathogens. However, a plasmid carried by virulent Yp encodes factors that dampen inflammation and debilitate phagocytes, thereby compromising cellular defense mechanisms. As such, plague vaccine researchers have devoted relatively little attention to cellular immunity. Here we review our recent work demonstrating that the passive transfer of primed T cells can suffice to protect mice against lethal intranasal Yp infection, a model of pneumonic plague. We also demonstrate that key elements of cellular immunity even play critical roles during antibody-mediated defense against plague. We conclude that next-generation plague vaccines should strive to prime both cellular and humoral immunity.