Protective Antimicrobial Effect of the Potential Vaccine Created on the Basis of the Structure of the IgA1 Protease from .

IgA1 protease is one of the virulence factors of , and other pathogens causing bacterial meningitis. The aim of this research is to create recombinant proteins based on fragments of the mature IgA1 protease A-P from serogroup B strain H44/76. These proteins are potential components of an antimeningococcal vaccine for protection against infections caused by pathogenic strains of and other bacteria producing serine-type IgA1 proteases. To obtain promising antigens for creating a vaccine, we designed and obtained several recombinant proteins. These proteins consisted of single or directly connected fragments selected from various regions of the IgA1 protease A-P. The choice of these fragments was based on our calculated data on the distribution of linear and conformational B-cell epitopes and MHC-II T-cell epitopes in the structure of IgA1 protease, taking into account the physicochemical properties of potential compounds and the results of a comparative analysis of the spatial structures of the original IgA1 protease and potential recombinant proteins. We studied the immunogenic and protective effects of the obtained proteins on the BALB/c mice against meningococci of serogroups A, B and C. Proteins MA-P-LEH, MW-K-LEH, MW-P-LEH, M(W-H)-(W-D)-(Y-P)-LEH and M(W-Q)-(Y-P)-LEH have shown the following antibody titers, 10/titer: 11 ± 1, 6 ± 2, 6 ± 1, 9 ± 1 and 22 ± 3, respectively. Also, the last two proteins have shown the best average degree of protection from serogroups A, B and C, %: 62 ± 6, 63 ± 5, 67 ± 4 respectively for M(W-H)-(W-D)-(Y-P)-LEH and 70 ± 5, 66 ± 6, 83 ± 3 respectively for M(W-Q)-(Y-P)-LEH. We selected two recombinant proteins consisting of two (M(W-Q)-(Y-P)-LEH) or three (M(W-H)-(W-D)-(Y-P)-LEH) linked fragments of IgA1 protease A-P as candidate active component for an antimeningococcal vaccine.