Recombinant outer membrane protein: a potential candidate for Th17 based vaccine against Klebsiella pneumonia (VAC4P.1066)

Abstract

Abstract Bacterial pneumonia is a leading cause of mortality and one major pathogen associated with this disease is Klebsiella pneumoniae (KP). Recently, the emergence of antibiotic resistant strains demands an effective vaccine against these bacteria. We have previously shown that intranasal immunization with heat-killed KP or crude outer membrane proteins (OMPs) isolated from KP induced antigen specific Th17 responses and these Th17 cells conferred serotype independent protection against various clinical isolates of K. pneumoniae including the recently described multidrug resistant New Delhi Metallo-beta-lactamase-1 strain. To develop a clinically relevant vaccine, we cloned individual OMPs from K. pneumoniae and successfully expressed OmpX in the BL21 E. coli. The purified recombinant OmpX was recognized by KP immune serum by direct ELISA and also recognized by Th17 cells from KP immunized mice. In vivo, intranasal immunization of the purified OmpX induced robust mucosal Th17 responses and left IL-17 producing gamma-delta T cells unaffected. In combination with a mucosal adjuvant, both intranasal and intramuscular immunization provided serotype independent protection against live bacterial challenge. Taken together, these data demonstrated that OMPs serves as an excellent candidate for the development of clinical relevant vaccines against K. penumoniae especially the newly emerged antibiotic-resistant strains that impose great threat to the public health.