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.

Specific Antibodies to the Fragments of Meningococcal IgA1 Protease during the Formation of Immunity to Bacterial Infections.

The features of individual fragments of IgA1 protease of Neisseria meningitidis serogroup B during the formation of immunity to bacterial infections in animals and humans were studied. The antibodies to the immunogenic regions of the studied proteins are also detected in mice infected with some bacterial pathogens and in humans with bacterial meningitis. A region of IgA1 protease was identified that is not capable of producing antibodies during immunization of animals, but that detects homologous antibodies in the blood of humans and animals recovered from bacterial infections.

Highly Similar Sequences of Mature IgA1 Proteases from , and .

The mature serine-type IgA1 protease from serogroup B strain H44/76 (IgA1pr1_28-1004) is considered here as the basis for creating a candidate vaccine against meningococcal meningitis. In this work, we examine the primary structure similarity of IgA1 proteases from various strains of a number of Gram-negative bacteria (, , ) in order to find a structural groundwork for creating a broad-spectrum vaccine based on fragments of this enzyme. BLAST has shown high similarity between the primary structure of IgA1pr1_28-1004 and hypothetical sequences of mature IgA1 proteases from (in 1060 out of 1061 examined strains), (in all 602 examined strains) and (in no less than 137 out of 521 examined strains).

Molecular dynamics complemented by site-directed mutagenesis reveals significant difference between the interdomain salt bridge networks stabilizing oligopeptidases B from bacteria and protozoa in their active conformations.

Oligopeptidases B (OpdBs) are trypsin-like peptidases from protozoa and bacteria that belong to the prolyl oligopeptidase (POP) family. All POPs consist of C-terminal catalytic domain and N-terminal β-propeller domain and exist in two major conformations: closed (active), where the domains and residues of the catalytic triad are positioned close to each other, and open (non-active), where two domains and residues of the catalytic triad are separated. The interdomain interface, particularly, one of its salt bridges (SB1), plays a role in the transition between these two conformations.