Vaccine-driven lung TRM cells provide immunity against

Tissue resident memory (TRM) cells are thought to play a role in lung mucosal immunity to pathogens, but strategies to elicit TRM by mucosal vaccines have not yet been fully realized. Here, we formulated a vaccine composed of outer membrane protein (Omp) X from K. pneumoniae and LTA1 adjuvant that was administered by the intrapulmonary route. This vaccine elicited both Th1 and Th17 cells that shared transcriptional features with cells elicited by heat-killed K. pneumoniae. Antibody responses were required to prevent bacterial dissemination but dispensable for lung-specific immunity. In contrast, lung immunity required CD4(+) T cells, STAT3 expression, and IL-17R signaling in fibroblasts. Lung-specific CD4(+) T cells from OmpX+LTA1 immunized mice were observed homing to the lung and could mediate protection against infection in an adoptive transfer model. Vaccine-elicited Th17 cells showed reduced plasticity and were resistant to the immunosuppressant FK506 compared with Th1 cells, and Th17 cells conferred protection under conditions of transplant immunosuppression. These data demonstrate a novel vaccine strategy that elicits lung TRM cells and promotes serotype-independent immunity to K. pneumoniae.