Strategic Development of a Poly-Epitopic Vaccine Employing Immunoinformatics Approach Against Uropathogenic Escherichia Coli Causing Urinary Tract Infections

Abstract

Some of the frequently occurring pathological conditions involve infections of the urinary tract (UTIs) and could be of both types; community-acquired and nosocomial. The uropathogenic E. coli (UPEC) stands among the primary causative agents of UTIs. The disease caused by UPEC is because of the presence of its multiple virulence factors which could either be structural (flagella etc.) or secreted (in terms of toxins) and adherence to host epithelial cells via biofilm formation. The usage of antibiotics is the routine therapy being used in various countries to treat UTIs but becoming ineffective because of increasing antibiotic resistance among UPEC strains. Thus, there must be the development of some alternative treatment strategies such as vaccine development against UTIs. In the following study, pan- genomics along with reverse vaccinology approaches are used under the framework of bioinformatics for the identification of core putative vaccine candidates, employing 62 UPEC genomes (complete and draft), available publicly. Total nine T-cell epitopes (derived from B-cells) of both MHC classes (I and II), were prioritized among three potential protein candidates. These epitopes were then docked together by using linkers and an adjuvant to form a poly-valent vaccine construct. The chimeric vaccine construct was undergone by molecular modelling, further refinement and minimization in its energy. The vaccine construct showed positive results in protein-protein interaction analysis by showing interaction with toll-like receptors. In future, these identified epitopes could be experimentally validated for the development of UPEC vaccine against UTIs.