Subtractive Proteomics and Reverse Vaccinology Strategies for Designing a Multiepitope Vaccine Targeting Membrane Proteins of Klebsiella pneumoniae

Klebsiella pneumoniae is a Gram-negative opportunistic pathogen that causes bacteremia, meningitis, endocarditis, cellulitis, urinary tract infections. The emergence of antibiotic resistance in this pathogen makes the infection of K. pneumoniae more dangerous. Therefore, it is the need of hour to use the advanced technologies for developing vaccines, which can surpass the traditional methods used for treating the infections. In our study, we have considered designing multi-epitope based vaccines targeting the outer membrane proteins of K. pneumoniae. The proteome of K. pneumoniae was analysed using subtractive proteomics, and reverse vaccinology. In subtractive proteomics, the proteins were sorted on the basis of SignalP, TatP, LIPOP, Transmembrane helicity (TMHMM, HMMTOP), and cellular localization (CELLO and PSORTb). Fifteen outer membrane protein were selected that had the potential for the multi-epitope based vaccine designing. The MHC I, MHC II, B cell interacting epitopes of these proteins, which could generate a decent cellular and humoral immune responses in the host cell, were analysed. On this basis, four vaccine constructs (VK1 to VK4) were analyzed for their antigenicity, allergenicity, solubility, and physicochemical properties. Out of these constructs, VK2 was modeled using RapotorX server and docked (PatchDock) with different HLA alleles, and its molecular dynamics was also studied. These analysis showed that VK2 multi-epitope vaccine could be a suitable target to control the K. pneumoniae infections.