Development of candidate vaccines against infection caused by shiga-toxin producing Escherichia coli. Part 2

Prevention and treatment of hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS) caused by Shiga-toxin producing Escherichia coli (STEC) continues to be a public health concern. The main reason for the problem is the lack of vaccines and lack of evidence for using of antibacterial etiotropic drugs to treat this infection. A promising scientific approach to create specific agents against STEC infection is the development of subunit recombinant vaccines. The analysis of experimental studies presented in this review shows that effective subunit vaccines against STEC infection can be created on the basis of known immunogenic determinants of HC and HUS causative agents – EspA, EspB, and Tir proteins, intimin, as well as H7 antigen of E. coli O157:H7 and nontoxic proteins of Shiga toxins Stx1 and Stx2 A and B subunits. Using these epitopes, three types of subunit vaccines are designed: antibacterial vaccine, vaccine protecting the macroorganism from systemic intoxication caused by Shiga toxins, and vaccines that simultaneously induce the antibacterial and antitoxic immunity. Since the epitopes listed above are weak immunogenic, to increase their immunogenicity, complex chimeric antigenic structures containing protein inducers are constructed that significantly increase the immune response to target specific epitopes. Mineral adjuvants are also widely used to increase the immunogenicity of STEC epitopes. All three types of created candidate subunit vaccines, at subcutaneous, intramuscular and intranasal application induce production of specific IgG and secretory IgA antibodies in animals and protect them from the infection caused by the STEC strains. Key words: STEC, hemorrhagic colitis, immunodominant antigens, Shiga toxins, EspA, EspB, Tir, intimine, IgG, sIgA