IgA1 Protease as a Vaccine Basis for Prevention of Bacterial Meningitis

Abstract

The review covers the study of the protective properties of IgA1 protease and the possibility of creating a vaccine preparation for the prevention of bacterial meningitis of various origins on its basis. Bacterial meningitis belongs to the group of socially dangerous diseases and is characterized by a severe course, numerous complications and high mortality. The approaches used at present in world practice to create antimicrobial vaccines are based on a narrow targeting against a specific pathogen. The development of a monocomponent vaccine against a wide range of bacterial pathogens with a common virulence factor is still relevant. IgA1 protease, a protein that is one of the main virulence factors of a number of gram-negative and gram-positive bacteria, can serve as such an antigen. Bacterial IgA1 protease is uniquely specific for immunoglobulins A1 (IgA1), cleaving peptide bonds in the hinge regions of the IgA1 in humans and other higher primates. Bacteria, getting on the mucous membrane, destroy IgA1, which acts as the first barrier to protect the body from infections. Neutralization of IgA1 protease at this stage can become an obstacle to the development of infection, hindering the adhesion of a number of pathogens that produce this protein. The data available in the literature on the mechanism of antibacterial protection are scattered and ambiguous. The review considers the literature data and the results of our own experiments on the protective activity of IgA1 protease. We have shown that the recombinant meningococcal IgA1 protease and some of its fragments protect mice from infection with a live virulent culture not only of meningococci of the main epidemic serogroups (A, B, C, and W135), but also of some of the most common virulent pneumococcal serotypes. The data obtained indicate the possibility of creating a monocomponent vaccine against these and, possibly, other bacterial infections. Currently, significant progress has been made in studying the structure and functions of secreted proteins in the bacteria Neisseria meningitidis and Haemophilus influenzae. In this review we describe protein translocation systems of N. meningitidis, which are related to the secretion of proteins in these bacteria, and also present modern data on the functions of these proteins. Analysis of experimental data on the structure of IgA1 protease of N. meningitidis and the formation of immunity during vaccination is of key importance in the development of prophylactic preparations.

Comparative Genomic Analysis of Non-typeable Haemophilus Influenzae in Children with Acute and Chronic Pneumonia versus Healthy Controls

“…The virulence factor of the protease class produced by the gene igA1 also showed differences between the acute and control groups, and this virulence factor is believed to be associated with the occurrence of meningitis[24]. Overall, the analysis conducted indicates that virulence factors may play a significant role in the variation of clinical phenotypes observed in NTHI.…”

Mechanisms of host manipulation by Neisseria gonorrhoeae

“…In addition to the role the gonococcal IgA1 protease has in promoting intracellular survival, this protease can also further reduce mucosal antibody levels by cleaving the hinge region of secretory IgA1 (Blake and Swanson, 1978;Johnson and Criss, 2011). However, despite extensive studies of the equivalent protein from meningococci (Brooks et al, 1992;Parsons et al, 2004;Tommassen and Arenas, 2017;Spoerry et al, 2021;Zhigis et al, 2021;Kilian et al, 2022), the role of the gonococcal IgA1 protease in antibody cleavage during infection has not been extensively studied. Although the IgA1 protease from vaginal washings in women with gonorrhoea demonstrated antibody cleavage activity in vitro (Blake et al, 1979), no activity has been noted in vivo to date (Hedges et al, 1998a).…”

Highly Similar Sequences of Mature IgA1 Proteases from Neisseria meningitidis, Neisseria gonorrhoeae and Haemophilus influenzae

“…We believe that the development of a single-component vaccine against a wide range of bacterial pathogens with a common virulence factor is still relevant, and the search for appropriate immunologically harmless protective antigens is an important research task [ 10 ].…”