Abstract
Klebsiella pneumoniae is an opportunistic gram-negative bacterium that causes nosocomial infection in healthcare settings. Despite the high morbidity and mortality rate associated with these bacterial infections, no effective vaccine is available to counter the pathogen. In this study, the pangenome of a total of 222 available complete genomes of K. pneumoniae was explored to obtain the core proteome. A reverse vaccinology strategy was applied to the core proteins to identify four antigenic proteins. These proteins were then subjected to epitope mapping and prioritization steps to shortlist nine B-cell derived T-cell epitopes which were linked together using GPGPG linkers. An adjuvant (Cholera Toxin B) was also added at the N-terminal of the vaccine construct to improve its immunogenicity and a stabilized multi-epitope protein structure was obtained using molecular dynamics simulation. The designed vaccine exhibited sustainable and strong bonding interactions with Toll-like receptor 2 and Toll-like receptor 4. In silico reverse translation and codon optimization also confirmed its high expression in E. coli K12 strain. The computer-aided analyses performed in this study imply that the designed multi-epitope vaccine can elicit specific immune responses against K. pneumoniae. However, wet lab validation is necessary to further verify the effectiveness of this proposed vaccine candidate.
Highlights
Klebsiella pneumoniae (K. pneumoniae) causes nosocomial infections, majorly infecting immunocompromised patients
Mortality rates associated with carbapenemase-producing K. pneumoniae infections reportedly vary from 22% to 72%, underlying the significant threat to human health posed by this opportunistic microorganism [2,3,4]
A total of 222 complete genomes and associated proteomes of K. pneumoniae were downloaded from the NCBI
Summary
Klebsiella pneumoniae (K. pneumoniae) causes nosocomial infections, majorly infecting immunocompromised patients. A number of pathological conditions are associated with this bacterial infection such as pneumonia, bacteremia, septicemia, endocarditis, meningitis, and cellulitis [1]. Carbapenemase-producing K. pneumoniae strains present a major problem from a clinical and epidemiological perspective. Mortality rates associated with carbapenemase-producing K. pneumoniae infections reportedly vary from 22% to 72%, underlying the significant threat to human health posed by this opportunistic microorganism [2,3,4]. Lipopolysaccharide (LPS) of K. pneumoniae has been used previously to develop vaccine but severe side effects associated with LPS-containing vaccines present a major problem [5]. Capsular polysaccharides (CPS) have been explored for vaccine preparation but CPS-based vaccines, nontoxic and immunogenic, contain many K-types (77 different antigens), which proves a Vaccines 2019, 7, 88; doi:10.3390/vaccines7030088 www.mdpi.com/journal/vaccines
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