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.

中文翻译：

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IgA1 蛋白酶作为预防细菌性脑膜炎的疫苗基础

摘要

该综述涵盖了对 IgA1 蛋白酶保护特性的研究，以及在此基础上制备预防各种起源细菌性脑膜炎的疫苗制剂的可能性。细菌性脑膜炎属于危害社会的一类疾病，其特点是病程严重、并发症多、死亡率高。目前在世界实践中用于制造抗微生物疫苗的方法是基于针对特定病原体的狭窄靶向。针对具有共同毒力因子的广泛细菌病原体的单组分疫苗的开发仍然具有相关性。IgA1 蛋白酶是一种蛋白质，它是许多革兰氏阴性和革兰氏阳性细菌的主要毒力因子之一，可用作此类抗原。细菌 IgA1 蛋白酶对免疫球蛋白 A1 (IgA1) 具有独特的特异性，可切割人类和其他高等灵长类动物 IgA1 铰链区中的肽键。进入粘膜的细菌会破坏 IgA1，后者是保护身体免受感染的第一道屏障。在这个阶段中和 IgA1 蛋白酶可能成为感染发展的障碍，阻碍产生这种蛋白质的许多病原体的粘附。文献中关于抗菌保护机制的数据是零散和模糊的。该综述考虑了文献数据和我们自己关于 IgA1 蛋白酶保护活性的实验结果。我们已经证明，重组脑膜炎球菌 IgA1 蛋白酶及其一些片段可以保护小鼠免受活毒培养物的感染，不仅是主要流行血清群（A、B、C 和 W135）的脑膜炎球菌，还包括一些最常见的脑膜炎球菌。常见的强毒肺炎球菌血清型。获得的数据表明有可能针对这些细菌感染以及可能的其他细菌感染制造单组分疫苗。目前，在研究细菌分泌蛋白的结构和功能方面取得了重大进展。脑膜炎奈瑟菌和流感嗜血杆菌。在这篇综述中，我们描述了脑膜炎奈瑟菌的蛋白质易位系统，这些系统与这些细菌中蛋白质的分泌有关，并且还提供了关于这些蛋白质功能的现代数据。对脑膜炎奈瑟球菌IgA1 蛋白酶结构和疫苗接种过程中免疫形成的实验数据的分析对于预防制剂的开发至关重要。