Vaccine Against Entheropathogenic E. coli: A Systematic Review

Enteric diseases are a major cause of childhood death in the developing world, ranking as the second cause of death in children. Enteropathogenic Escherichia coli(EPEC) are important diarrheal pathogens of children under 5 years of age. Due to high mortality, several international organizations such as the WHO and UNICEF have dedicated preventive and control programs for diarrheal diseases. Among the suggested initiatives aiming to prevent infectious diarrhea include vaccine development and improvement in sanitation and water and food supplies. Upon contact with host cells, EPEC delivers an array of virulence protein factors, which integrated actions interferes with the normal adjusting the targets molecular cell functions leading to diarrhea. The locus of entherocyte effacement (LEE)pathogenicity island contains genes encoding synthesis of the EPEC virulence factors membrane adhesin intimin, T3SS (Esc and Sep proteins), chaperones (Ces proteins), translocators (EspA, EspB, and EspD), effector proteins (EspF, EspG, EspH, Map and EspZ), the translocated intimin receptor (Tir), and the regulatory protein Ler (LEEencoded regulator).Bundle-forming pilus (BfpA) is another virulence factor that mediates the initial contact between EPEC and the host cell. BfpA is encoded by a gene localized on a 50–70 MDa plasmid and is designated as EPEC adherence factor (EAF). BfpA, intimin and translocated Tir initiate EPEC infection. This repertoire of virulence factors offers strategic epitopes as vaccine candidates. Employing the proposed technologies for modern vaccines, recombinant Mycobacterium smegmatis (Smeg) and Mycobacterium bovis BCG strains were constructed to express BfpA, intimin and EspA. Recombinant clones were selected based on kanamycin resistance. Recombinant proteins are immunogenic, and the resultant antibodies recognize and block EPEC adhesion onto HEp-2 target cells. In attention to regulatory agency recommendations, kanamycin should not be used to produce rBCG expressing the E. coli EPEC virulence factors BfpA, intimin and EspA. Accordingly, an expression system with a Pasteur auxotrophic BCG mutant for leucine (BCG Pasteur ΔleuD) and a replicative vector (pUP410)should be used. Obtained recombinants will be grown in large scale, and their immunogenic effectivity and human safety submitted to WHO indicated quality controls.