Вопросы вирусологии. 2021; 66: 399-408
Мукозальный иммунитет и вакцины против вирусных инфекций
https://doi.org/10.36233/0507-4088-82Аннотация
Иммунитет слизистых оболочек (СО) реализуется через структурно-функциональную систему, называемую мукозо-ассоциированной лимфоидной тканью (МАЛТ; mucosa-associated lymphoid tissue, MALT). МАЛТ подразделяется на части (кластеры) в зависимости от их анатомического расположения, однако все они имеют идентичное строение: слой слизи, эпителиальная ткань, собственная пластинка СО и лимфоидные фолликулы. Плазматические клетки МАЛТ вырабатывают уникальный тип иммуноглобулинов (Ig) – IgA, обладающий способностью к полимеризации. При мукозальной иммунизации преобладающей формой этих антител (АТ) является секреторный димер (sIgA), в больших количествах концентрирующийся в СО. Мукозальные IgA действуют как первая линия защиты и эффективно нейтрализуют вирусные агенты на уровне входных ворот инфекции, предотвращая поражение эпителиальных клеток и генерализацию инфекционного процесса. На сегодняшний день лицензированы несколько мукозальных противовирусных вакцин, в состав которых входят аттенуированные штаммы соответствующих вирусов: полиомиелита, гриппа, ротавируса. Несмотря на огромные успехи, достигнутые с применением этих вакцинных препаратов, в частности по ликвидации полиомиелита, существенными недостатками использования аттенуированных вирусных штаммов, входящих в их состав, являются риск реактогенности и возможность реверсии к вирулентному штамму в процессе вакцинации. Тем не менее именно мукозальная вакцинация, имитируя естественное инфицирование, способна индуцировать быстрый и эффективный иммунный ответ и таким образом способствовать предотвращению, а возможно, и остановке вспышек многих вирусных инфекций. В настоящее время клинические испытания успешно проходит целый ряд интраназальных вакцин, основанных на новом векторном подходе, при котором для доставки протективно значимых иммуногенов патогенных вирусов используются безопасные вирусные векторы. Самым тестируемым вектором для интраназальных вакцинных препаратов является аденовирус, а наиболее значимым иммуногеном – S-белок SARSCoV-2. Исследуются также мукозальные векторные вакцины против респираторно-синцитиального вируса человека и вируса иммунодефицита человека 1 типа на основе вируса Сендай, способного бессимптомно реплицироваться в клетках бронхиального эпителия.
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Problems of Virology. 2021; 66: 399-408
Mucosal immunity and vaccines against viral infections
https://doi.org/10.36233/0507-4088-82Abstract
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.
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25. Huang F.S., Bernstein D.I., Slobod K.S., Portner A., Takimoto T., Russell S.J., et al. Safety and immunogenicity of an intranasal Sendai virus-based vaccine for human parainfluenza virus type I and respiratory syncytial virus (SeVRSV) in adults. Hum. Vaccin. Immunother. 2021; 17(2): 554–9. https://doi.org/10.1080/21645515.2020.1779517
26. Tasker S., O’Rourke A.N., Suyundikov A., Booth P.-G.J., Bart S., Krishnan V., et al. Safety and immunogenicity of a novel intranasal influenza vaccine (NasoVAX): A phase 2 randomized, controlled trial. Vaccines. 2021; 9(3): 224. https://doi.org/10.3390/vaccines9030224
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28. King R.G., Silva-Sanchez A., Peel J.N., Botta D., Dickson A.M., Pinto A.K., et al. Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 and fully protects mice from lethal challenge. Vaccines (Basel). 2021; 9(8): 881. https://doi.org/10.3390/vaccines9080881
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33. Gallo O., Locatello L.G., Mazzoni A., Novelli L., Annunziato F. The central role of the nasal microenvironment in the transmission, modulation, and clinical progression of SARS-CoV-2 infection. Mucosal Immunol. 2020; 14(2): 305–16. https://doi.org/10.1038/s41385-020-00359-2
34. Moreno-Fierros L., García-Silva I., Rosales-Mendoza S. Development of SARS-CoV-2 vaccines: should we focus on mucosal immunity? Expert. Opin. Biol. Ther. 2020; 20(8): 831–6. https://doi.org/10.1080/14712598.2020.1767062
35. Mudgal R., Nehul S., Tomar S. Prospects for mucosal vaccine: shutting the door on SARS-CoV-2. Hum. Vaccin. Immunother. 2020; 16(12): 2921–31. https://doi.org/10.1080/21645515.2020.1805992
