Immunity of a Klebsiella Pneumoniae Vaccine Independent of Antigen Specific Antibody

Abstract

Abstract Objective We demonstrated the serotype independent immunity of Klebsiella pneumoniae (K. pneumoniae) vaccine. We would like to declare next if the noble effect is dependent on the antibody specific manner. Methods Mice were vaccinated via intranasal with Kp serotype 2 OMPx adjuvanted with heat-labile enterotoxin A1 domain (LTA1) and boosted at 3 weeks after the initial immunization. Protective immunity was compared among the C57Bl/6 mice, STAT3 fl/fl×CD4 Cre mice, and Il21r −/− mice by infecting with K1 strain of K. pneumoniae. Lung T-cell responses were evaluated by FACS and ELISPOT as well as K1 strain specific antibodies were assessed by ELISA. Results CD4+ T-cells of the vaccinated lungs in the CD4+ STAT3 deficient mice were significantly decreased compared to the WT mice and the Il21r −/− mice, and IL17A response by ELISPOT were significantly reduced as well. Meanwhile, K1 strain specific IgG in the serum and IgA in the lung homogenates of vaccinated WT mice were significantly increased in vaccinated mice and these responses were reduced in vaccinated CD4+ STAT3 deficient mice and Il21r −/− mice. Furthermore, vaccine induced protection was compromised in vaccinated CD4+ STAT3 deficient mice whereas the protection as well as antigen elicited lung IL-17 responses were maintained in Il21r −/− mice. Conclusions STAT3 activation in CD4+ T-cells regulated by IL-21R signaling are required for the K. pneumoniae specific antibodies, but these antibody responses were dispensable for the serotype independent immunity LTA1 adjuvanted K. pneumoniae vaccine. However, CD4 STAT3 was essential for Th17 immunity and therapeutic efficacy of the vaccine.