Journal of Clinical PracticeJournal of Clinical PracticeКлиническая практика2220-30952618-8627Eco-Vector11112010.17816/clinpract111120ReviewsНаучные обзорыReview ArticleA rational strategy for the maintenance of antiviral immunity to new SARS-CoV-2 strainsРациональная стратегия поддержания противовирусного иммунитета к новым вариантам SARS-CoV-2https://orcid.org/0000-0003-1039-42453968-2971BaklaushevVladimir P.БаклаушевВладимир Павлович
Russian Federation

MD, PhD

д.м.н.

baklaushev.vp@fnkc-fmba.ruhttps://fnkc-fmba.ru/about/komanda-upravleniya/https://orcid.org/0000-0003-3056-48891559-5866YusubalievaGaukhar M.ЮсубалиеваГаухар Маратовна
Russian Federation

MD, PhD

к.м.н.

gaukhar@gaukhar.orghttps://orcid.org/0000-0001-8461-48676524-9947BychininMikhail V.БычининМихаил Владимирович
Russian Federation

MD, PhD

к.м.н.

drbychinin@gmail.comhttps://orcid.org/0000-0002-8258-8148YusubalievaSaule M.ЮсубалиеваСауле Маратовна
Kazakhstan
sm_yusubalieva@mail.ruhttps://orcid.org/0000-0003-2705-35781046-8801KalsinVladimir A.КальсинВладимир Анатольевич
Russian Federation
vkalsin@mail.ruhttps://orcid.org/0000-0003-2143-86962670-6662TroitskiyAleksandr V.ТроицкийАлександр Витальевич
Russian Federation

MD, PhD

д.м.н.

dr.troitskiy@gmail.comFederal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of the Federal Medical Biological AgencyФедеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий Федерального медико-биологического агентства РоссииPulmonology Scientific Research Institute under Federal Medical and Biological Agency of Russian FederationНаучно-исследовательский институт пульмонологииEngelhardt Institute of Molecular Biology of the Russian Academy of SciencesИнститут молекулярной биологии имени В.А. ЭнгельгардтаFederal Scientific and Clinical Center for Specialized Medical Assistance and Medical Technologies of the Federal Medical Biological AgencyФедеральный научно-клинический центр специализированных видов медицинской помощи и медицинских технологий Федерального медико-биологического агентства РоссииAstana Medical UniversityМедицинский университет Астана2610202213343552909202229092022Copyright ©; 2022, Baklaushev V.P., Yusubalieva G.M., Bychinin M.V., Yusubalieva S.M., Kalsin V.A., Troitskiy A.V.Copyright ©; 2022, Баклаушев В.П., Юсубалиева Г.М., Бычинин М.В., Юсубалиева С.М., Кальсин В.А., Троицкий А.В.2022Baklaushev V.P., Yusubalieva G.M., Bychinin M.V., Yusubalieva S.M., Kalsin V.A., Troitskiy A.V.Баклаушев В.П., Юсубалиева Г.М., Бычинин М.В., Юсубалиева С.М., Кальсин В.А., Троицкий А.В.https://creativecommons.org/licenses/by-nc-nd/4.0https://clinpractice.ru/clinpractice/article/view/111120

New variants of SARS-CoV-2 such as Omicron BA.2, BA.4/5, BA.2.12.1 and BA 2.75 are characterized by higher infectivity and the ability to escape virus-neutralizing antibodies against previous coronavirus variants. The S-trimer of BA.2 and its phylogenetic derivatives are characterized by a predominant «Up»-conformation, which facilitates the interaction with ACE2 on target cells and promotes the resistance to neutralizing antibodies. The immunity acquired from the infection with earlier strains is non-sterile for both early and later strains; the booster systemic immunization does not significantly affect the effectiveness of antiviral immunity, and its feasibility is currently being questioned. Studies of the mucosal immune response have shown that intranasal immunization with adenovirus vaccines provides more pronounced protective immunity than systemic reimmunization does. A promising approach is the creation of multivalent inhaled next generation vaccines containing immunoadjuvants that activate B- and T-cell mucosal immunity. Currently, a large number of intranasal vaccines are undergoing phase I/II trials, while the preclinical and preliminary clinical results indicate that this method of vaccination provides a better mucosal immune response at the entry site of the virus than systemic immunization does. This strategy may provide a long-term immune protection against the currently existing and yet unknown new strains of SARS-CoV-2.

Новые варианты вируса SARS-CoV-2 Омикрон BA.2, BA.4/5, BA.2.12.1 и BA.2.75 характеризуются более высокой заразностью и способностью ускользать от вируснейтрализующих антител, выработанных против других, более ранних вариантов коронавируса. S-тример BA.2 и его филогенетических потомков характеризуется преимущественным конформационным Uр-положением, облегчающим взаимодействие с ACE2 на клетках-мишенях. Иммунитет, приобретаемый в результате инфицирования SARS-CoV-2, является нестерильным как для ранних, так и для более поздних вариантов вируса; бустерная системная иммунизация значимо не влияет на эффективность защитного иммунитета против новых штаммов, и в настоящее время ее целесообразность ставится под сомнение. Исследования мукозального иммунного ответа показали, что интраназальная иммунизация аденовирусными вакцинами способствует выработке большего защитного иммунитета, чем системная реиммунизация, как с точки зрения титра секреторных IgA, обеспечивающих элиминацию вируса со слизистых оболочек, так и в плане активации специфических клонов Т-клеток. Для обеспечения последнего может иметь значение не только иммунизация S-белком, но и дополнительная интраназальная иммунизация N-белком, активирующая большее количество клонов Т-клеток, распознающих соответствующие консервативные пептидные эпитопы N-белка. Перспективным является создание мультивалентных ингаляционных вакцин, содержащих иммуноадъюванты, активирующие В- и Т-клеточный ответ в бронхоальвеолярном дереве. В настоящее время большое количество интраназальных вакцин проходит испытание I/II фазы: доклинические и предварительные клинические результаты свидетельствуют о том, что при таком способе вакцинации иммунный ответ в месте входа вируса — на слизистых оболочках — осуществляется гораздо более эффективно, чем при системной иммунизации. Эта стратегия может обеспечить продолжительную иммунную защиту от уже существующих и еще неизвестных новых штаммов SARS-CoV-2.

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