Protective efficacy of two novel Klebsiella pneumoniae vaccine antigens, LysM/BON and OMPP1, in a murine model

Klebsiella pneumoniae, a multidrug-resistant Gram-negative bacterium, is a major opportunistic pathogen that causes septicaemia as well as respiratory, urinary tract, and soft tissue infections. Infections are difficult to treat and often associated with high mortality rates. Currently, there are no approved vaccines against K. pneumoniae. Previously, we developed a proteomic cell-blot approach to identify bacterial proteins involved in host cell attachment as potential vaccine antigens against Burkholderia spp., Pseudomonas aeruginosa, and verocytotoxigenic Escherichia coli. In this work, using the same approach, we have identified 31 bacterial proteins that contribute to K. pneumoniae attachment to host epithelial cells. Two of them, LysM/BON and OMPP1, were selected for further evaluation as vaccine candidates. E. coli BL21 cells expressing recombinant LysM/BON or OMPP1 demonstrated increased levels of attachment to 16HBE14o⁻ cells. Furthermore, immunisation with both proteins conferred protection against sepsis in a C57BL/6 mouse model of K. pneumoniae infection. Immunisation with OMPP1 or LysM/BON showed 2.69 log₁₀ and 1.54 log₁₀ CFU reductions in bacterial burden, respectively, and also reduced dissemination to the spleen. The antigens stimulated distinct antigen-specific recall response profiles; however, both antigens induced IL-17 and IL-22 expression, especially in NK cells, suggesting that these cytokines may be important in stimulating protection against K. pneumoniae. Both novel antigens have a high potential to be developed as protective vaccine against K. pneumoniae infection.