Using reverse vaccinology to construct multi-epitope subunit vaccine candidates for Klebsiella pneumoniae

Klebsiella pneumoniae (K. pneumoniae) is a Gram-negative clinically relevant pathogen responsible for causing nosocomial infections. This bacterium is resistant to a spectrum of antibiotics and has been listed under "critical" priority for research and development of new antibiotics and alternative strategies. Reverse vaccinology was used to construct multiepitope vaccine candidates against six K. pneumoniae outer membrane proteins. Predicted B- and T-cell epitopes were evaluated using various bioinformatic tools to confirm their antigenic and non-allergenic nature. Additionally, the global population coverage of the epitopes was observed to be 75% as per in silico analysis. These epitopes were then used for the design and in silico characterization of seven multiepitope vaccine candidates. Molecular docking and simulation studies demonstrated that 5 out of the 7 vaccine candidates formed strong stable interactions with TLR2 and TLR4. Furthermore, in silico immunization simulations demonstrated the ability of these candidates to elicit effective immune responses. Lastly, high codon adaptation Index (CAI) values ensured that the candidates can be expressed in the Escherichia coli K12 host system following codon optimized multiepitope cloning. Importantly, the high antigenicity and global coverage of the combined construct represents a novel combination not previously reported. Based on our findings, the designed multiepitope vaccine candidates have potential as a vaccination strategy against K. pneumoniae.