Cell-Mediated Protection against PulmonaryYersinia pestisInfection

Pulmonary infection with the bacteriumYersinia pestis causes pneumonic plague, an often-fatal disease for which no vaccine is presently available. Antibody-mediated humoral immunity can protect mice against pulmonaryY. pestis infection, an experimental model of pneumonic plague. Little is known about the protective efficacy of cellular immunity. We investigated the cellular immune response toY. pestis in B-cell-deficient μMT mice, which lack the capacity to generate antibody responses. To effectively prime pulmonary cellular immunity, we intranasally vaccinated μMT mice with live replicatingY. pestis . Vaccination dramatically increased survival of μMT mice challenged intranasally with a lethalY. pestis dose and significantly reduced bacterial growth in pulmonary, splenic, and hepatic tissues. Vaccination also increased numbers of pulmonary T cells, and administration of T-cell-depleting monoclonal antibodies at the time of challenge abrogated vaccine-induced survival. Moreover, the transfer ofY. pestis -primed T cells to naive μMT mice protected against lethal intranasal challenge. These findings establish that vaccine-primed cellular immunity can protect against pulmonaryY. pestis infection and suggest that vaccines promoting both humoral and cellular immunity will most effectively combat pneumonic plague.