The Development of Klebsiella Pneumoniae Vaccine Strategy via Eliciting the Serotype-Independent Immunity in the Lung

Multidrug-resistant of Klebsiella pneumoniae (K. pneumoniae) has emerged as a global threat. Vaccination for at high-risk populations could be a promising strategy to prevent and control the disease. Mice were vaccinated via intranasal with a monovalent vaccine encoding Kp serotype 2 OMPx or a quadrivalent vaccine encoding OmpC, OmpW, Omplolb, and Omp36k, adjuvanted with heat-labile enterotoxin A1 domain (LTA1). Protective immunity was assessed by performing a pulmonary challenge with a heterologous mucoid serotype K1 strain of K. pneumoniae. Lung T-cell responses were evaluated mainly by FACS, ELISPOT, and LUMINEX. We also examined inflammatory cell changes by hematoxylin-eosin stain and immunofluorescence. Flow cytometry and ELISPOT analysis revealed that CD4+ T cells were significantly increased in the lungs of the monovalent or quadrivalent vaccinated mice and that a considerable fraction of them produced IL17A. And the supernatant of these cells also showed the significant production of IL-17A. Importantly, vaccinated mice showed a significant decrease in CFU in the lung and spleen, compared with mock-vaccinated mice. Finally, we observed that only lungs of intranasally vaccinated mice had lymphocytic structures around bronchi and vessels. Characterization of these structures by immunofluorescence confirmed the presence of inducible bronchus-associated lymphoid tissue (iBALT) – a structure that can not only support local induction of protective immunity but provide a long-term niche for vaccine-induced lymphocytes. These data support the therapeutic value of intranasal vaccination strategies to prevent K. pneumoniae infections.