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[黏膜免疫与抗病毒感染疫苗]

[Mucosal immunity and vaccines against viral infections].

作者信息

Zainutdinov S S, Sivolobova G F, Loktev V B, Kochneva G V

机构信息

FSBI State Scientific Center of Virology and Biotechnology «Vector» of the Federal Service for Surveillance of Consumer Rights Protection and Human Welfare (Rospotrebnadzor).

出版信息

Vopr Virusol. 2022 Jan 8;66(6):399-408. doi: 10.36233/0507-4088-82.

Abstract

Mucosal immunity is realized through a structural and functional system called mucose-associated lymphoid tissue (MALT). MALT is subdivided into parts (clusters) depending on their anatomical location, but they all have a similar structure: mucus layer, epithelial tissue, lamina propria and lymphoid follicles. Plasma cells of MALT produce a unique type of immunoglobulins, IgA, which have the ability to polymerize. In mucosal immunization, the predominant form of IgA is a secretory dimer, sIgA, which is concentrated in large quantities in the mucosa. Mucosal IgA acts as a first line of defense and neutralizes viruses efficiently at the portal of entry, preventing infection of epithelial cells and generalization of infection. To date, several mucosal antiviral vaccines have been licensed, which include attenuated strains of the corresponding viruses: poliomyelitis, influenza, and rotavirus. Despite the tremendous success of these vaccines, in particular, in the eradication of poliomyelitis, significant disadvantages of using attenuated viral strains in their composition are the risk of reactogenicity and the possibility of reversion to a virulent strain during vaccination. Nevertheless, it is mucosal vaccination, which mimics a natural infection, is able to induce a fast and effective immune response and thus help prevent and possibly stop outbreaks of many viral infections. Currently, a number of intranasal vaccines based on a new vector approach are successfully undergoing clinical trials. In these vaccines, the safe viral vectors are used to deliver protectively significant immunogens of pathogenic viruses. The most tested vector for intranasal vaccines is adenovirus, and the most significant immunogen is SARSCoV-2 S protein. Mucosal vector vaccines against human respiratory syncytial virus and human immunodeficiency virus type 1 based on Sendai virus, which is able to replicate asymptomatically in cells of bronchial epithelium, are also being investigated.

摘要

黏膜免疫是通过一个称为黏膜相关淋巴组织(MALT)的结构和功能系统来实现的。MALT根据其解剖位置可细分为不同部分(簇),但它们都具有相似的结构:黏液层、上皮组织、固有层和淋巴滤泡。MALT的浆细胞产生一种独特类型的免疫球蛋白IgA,其具有聚合能力。在黏膜免疫中,IgA的主要形式是分泌性二聚体sIgA,它大量集中在黏膜中。黏膜IgA作为第一道防线,在病毒进入门户处有效地中和病毒,防止上皮细胞感染和感染扩散。迄今为止,已有几种黏膜抗病毒疫苗获得许可,其中包括相应病毒的减毒株:脊髓灰质炎病毒、流感病毒和轮状病毒。尽管这些疫苗取得了巨大成功,特别是在根除脊髓灰质炎方面,但在其组成中使用减毒病毒株存在显著缺点,即有发生反应原性的风险以及在疫苗接种过程中可能回复为毒株的可能性。然而,正是模仿自然感染的黏膜疫苗能够诱导快速有效的免疫反应,从而有助于预防并可能阻止许多病毒感染的爆发。目前,一些基于新载体方法的鼻内疫苗正在成功进行临床试验。在这些疫苗中,使用安全的病毒载体来递送致病病毒的具有保护性的重要免疫原。用于鼻内疫苗的最常测试的载体是腺病毒,最重要的免疫原是SARS-CoV-2 S蛋白。基于仙台病毒的针对人类呼吸道合胞病毒和1型人类免疫缺陷病毒的黏膜载体疫苗也在研究中,仙台病毒能够在支气管上皮细胞中无症状复制。

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