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

Background/Objectives: IgA1 protease is one of the virulence factors of Neisseria meningitidis, Haemophilus influenzae and other pathogens causing bacterial meningitis. The aim of this research is to create recombinant proteins based on fragments of the mature IgA1 protease A²⁸–P¹⁰⁰⁴ from N. meningitidis serogroup B strain H44/76. These proteins are potential components of an antimeningococcal vaccine for protection against infections caused by pathogenic strains of N. meningitidis and other bacteria producing serine-type IgA1 proteases. Methods: 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 A²⁸–P¹⁰⁰⁴. 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. Results: Proteins MA²⁸–P¹⁰⁰⁴-LEH₆, MW¹⁴⁰–K⁸³³-LEH₆, MW³²⁹–P¹⁰⁰⁴-LEH₆, M(W¹⁴⁰–H³²⁸)-(W⁴¹²–D⁶⁰⁴)-(Y⁸⁶⁶–P¹⁰⁰⁴)-LEH₆ and M(W¹⁴⁰–Q²⁹⁹)-(Y⁸⁶⁶–P¹⁰⁰⁴)-LEH₆ have shown the following antibody titers, 10³/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 N. meningitidis serogroups A, B and C, %: 62 ± 6, 63 ± 5, 67 ± 4 respectively for M(W¹⁴⁰–H³²⁸)-(W⁴¹²–D⁶⁰⁴)-(Y⁸⁶⁶–P¹⁰⁰⁴)-LEH₆ and 70 ± 5, 66 ± 6, 83 ± 3 respectively for M(W¹⁴⁰–Q²⁹⁹)-(Y⁸⁶⁶–P¹⁰⁰⁴)-LEH₆. Conclusions: We selected two recombinant proteins consisting of two (M(W¹⁴⁰–Q²⁹⁹)-(Y⁸⁶⁶–P¹⁰⁰⁴)-LEH₆) or three (M(W¹⁴⁰–H³²⁸)-(W⁴¹²–D⁶⁰⁴)-(Y⁸⁶⁶–P¹⁰⁰⁴)-LEH₆) linked fragments of IgA1 protease A²⁸–P¹⁰⁰⁴ as candidate active component for an antimeningococcal vaccine. [ABSTRACT FROM AUTHOR]