mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-EOC-2515mimmun-2515Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESВлияние вакцинации от COVID-19 на иммунный статус и профиль аутоантител у женщин репродуктивного возрастаEffect of COVID-19 vaccination on the immune status and autoantibody profile in women of reproductive agehttps://orcid.org/0000-0002-4927-3590ДовганьА. А.DovganA. A.

аспирант

Москва

Postgraduate Student

Moscow

lina.dovgan@gmail.comhttps://orcid.org/0000-0002-0545-1607ДрапкинаЮ. С.DrapkinaYu. S.

к.м.н., врач – акушер-гинеколог

Москва

PhD (Medicine), Obstetrician-Gynecologist

Moscow

yu_drapkina@oparina4.ruhttps://orcid.org/0000-0003-1116-138XДолгушинаН. В.DolgushinaN. V.

д.м.н., профессор, заместитель директора – руководитель департамента организации научной деятельности

Москва

PhD, MD (Medicine), Professor, Head, Department of Organization of Scientific Activities, Deputy Director

Moscow

n_dolgushina@oparina4.ruhttps://orcid.org/0000-0002-5385-0370МенжинскаяИ. В.MenzhinskayaI. V.

Менжинская Ирина Владимировна, д.м.н., ведущий научный сотрудник

117997, Москва, ул. Академика Опарина, 4Тел.: 8 (495) 438-11-83Факс: 8 (495) 438-49-65

Menzhinskaya Irina V. PhD, MD (Medicine), Leading Research Associate

117997, Moscow, Acad. Oparin str., 4Phone: 7 (495) 438-11-83Fax: 7 (495) 438-49-65

i_menzinskaya@oparina4.ruhttps://orcid.org/0000-0001-9878-3637ИнвияеваЕ. В.InviyaevaE. V.

к.м.н., старший научный сотрудник

Москва

PhD (Medicine), Senior Research Associate

Moscow

e_inviyaeva@oparina4.ruhttps://orcid.org/0000-0002-8406-3206ВторушинаВ. В.VtorushinaV. V.

к.м.н., врач клинической лабораторной диагностики

Москва

PhD (Medicine), Doctor of Clinical Laboratory Diagnostics

Moscow

v_vtorushina@oparina4.ruhttps://orcid.org/0000-0001-5023-3476КречетоваЛ. В.KrechetovaL. V.

д.м.н., заведующая лабораторией клинической иммунологии

Москва

PhD, MD (Medicine), Head, Laboratory of Clinical Immunology

Moscow

l_krechetova@oparina4.ruhttps://orcid.org/0000-0003-0214-1213СухихГ. Т.SukhikhG. T.

д.м.н., профессор, академик РАН, директор

Москва

PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Director

Moscow

g_sukhikh@oparina4.ruФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова» Министерства здравоохранения РФРоссияV. Kulakov National Medical Research Center for Obstetrics, Gynecology and PerinatologyRussian Federation202231102022245979992Copyright © Довгань А.А., Драпкина Ю.С., Долгушина Н.В., Менжинская И.В., Инвияева Е.В., Вторушина В.В., Кречетова Л.В., Сухих Г.Т., 20222022Довгань А.А., Драпкина Ю.С., Долгушина Н.В., Менжинская И.В., Инвияева Е.В., Вторушина В.В., Кречетова Л.В., Сухих Г.Т.Dovgan A.A., Drapkina Y.S., Dolgushina N.V., Menzhinskaya I.V., Inviyaeva E.V., Vtorushina V.V., Krechetova L.V., Sukhikh G.T.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2515

В условиях пандемии COVID-19 растет научный интерес к изучению влияния предлагаемой вакцинации на репродуктивное здоровье женщин. Как известно, изменение состояния иммунной системы и активация аутоиммунного ответа могут привести к нарушению репродуктивной функции у женщин и потенциальным осложнениям последующей беременности. Цель – оценить влияние вакцины «Гам-КОВИД-Вак» на показатели иммунного статуса, связь их изменений и специфического иммунного ответа на вакцинацию с динамикой уровня аутоантител у женщин репродуктивного возраста.

В проспективное исследование включили 120 женщин, которым проводилась вакцинация от COVID-19 вакциной «Гам-КОВИД-Вак». Критериями включения в исследование были: возраст от 18 до 49 лет, отсутствие в анамнезе COVID-19, отрицательный результат исследования на SARS-CoV-2 методом ПЦР и отрицательные результаты тестов на антитела классов G и М к SARS-CoV-2 перед вакцинацией, отсутствие беременности и серьезных соматических заболеваний. Обследование пациенток проводилось дважды: непосредственно перед вакцинацией и через 90-100 дней после введения 1-го компонента вакцины. Уровень IgG-антител к SARS-CoV-2 после вакцинации оценивали с помощью ИФА. До и после вакцинации определяли уровни антифосфолипидных, антиядерных, органоспецифических и антигормональных аутоантител, проводили иммунофенотипирование лимфоцитов периферической крови с определением основных субпопуляций (CD3, CD4, CD8, CD19, CD5, CD16, CD56), а также экспрессии активационных маркеров лимфоцитов (HLA-DR, CD25, CD147) с использованием моноклональных антител.

Эффективность и безопасность комбинированной векторной вакцины от COVID-19 были высокими. Специфические IgG-антитела к SARS-CoV-2 продуцировались у 98,3% вакцинированных женщин, не наблюдалось серьезных побочных реакций. После вакцинации отмечалось повышение уровня некоторых аутоантител в пределах референсных диапазонов, только IgM-антитела к фосфатидилэтаноламину (ФЭ) и IgG-антитела к ДНК повысились выше референсных значений. Однако это повышение было транзиторным. После вакцинации наблюдались изменения параметров иммунограммы: повышение содержания в периферической крови клеток с фенотипом CD3+CD25+, CD19+ и уменьшение содержания клеток с фенотипом CD56+CD16+ в пределах референсных диапазонов, снижение показателя CD147+/CD3+. Между данными изменениями показателей иммунограммы и уровнем некоторых аутоантител была отмечена слабая корреляционная связь. Специфический противовирусный иммунный ответ на вакцинацию не коррелировал с аутоиммунным ответом.

Вакцинация «Гам-КОВИД-Вак» является эффективной, безопасной и не приводит к нарушениям в иммунной системе. Наблюдаемое повышение уровня аутоантител к ФЭ и ДНК носит транзиторный характер. Изменения параметров иммунного статуса в пределах референсных диапазонов могут быть обусловлены вакцинацией и выработкой специфического противовирусного иммунного ответа.

In the context of the COVID-19 pandemic, scientific interest is growing in studying the impact of the proposed vaccination on women’s reproductive health. As is known, alterations in the state of the immune system and activation of an autoimmune response can lead to reproductive failure in women and potential complications of subsequent pregnancy. Objective: to evaluate the effect of the “Gam-COVID-Vac” on the immune status parameters, the relationship of their changes and the specific immune response to vaccination with the dynamics of the level of autoantibodies in women of reproductive age.

The prospective study included 120 women who were vaccinated against COVID-19 with the “Gam-COVIDVac”. The criteria for inclusion in the study were: the age from 18 to 49 years, the absence of COVID-19 in the anamnesis, a negative result of a study on SARS-CoV-2 by PCR and negative results of tests for antibodies of classes G and M to SARS-CoV-2 before vaccination, the absence of pregnancy and serious somatic diseases. The patients were examined twice: immediately before vaccination and 90-100 days after the introduction of the 1st component of the vaccine. The level of IgG antibodies to SARS-CoV-2 after vaccination was assessed using ELISA. Before and after vaccination, the levels of antiphospholipid, anti-nuclear, organ-specific and antihormonal autoantibodies were determined, peripheral blood lymphocytes were immunophenotyped to determine the main subpopulations (CD3, CD4, CD8, CD19, CD5, CD16, CD56), as well as the expression of activation markers of lymphocytes (HLA-DR, CD25, CD147) using monoclonal antibodies.

The effectiveness and safety of the combined vector vaccine against COVID-19 were high. Specific IgG antibodies to SARS-CoV-2 were produced in 98.3% of vaccinated women, no serious adverse reactions were observed. After vaccination, there was an increase in the level of some autoantibodies within the reference ranges, only IgM antibodies to phosphatidylethanolamine (PE) and IgG antibodies to DNA increased above the reference values. However, this increase was transient. After vaccination, the following changes in the parameters of the immunogram were observed: an increase in the content of cells with CD3+CD25+, CD19+ phenotype in peripheral blood and a decrease in the content of cells with CD56+CD16+ phenotype within the reference ranges, a decrease in CD147+/CD3+. Weak correlations were noted between these changes in immunogram parameters and the levels of some autoantibodies. The specific antiviral immune response to vaccination did not correlate with the autoimmune response.

Vaccination with “Gam-COVID-Vac” is effective and safe and does not lead to disorders in the immune system. The observed increase in the level of autoantibodies to PE and DNA is transient. Changes in the parameters of the immune status within the reference ranges may be due to vaccination and the development of a specific antiviral immune response.

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The authors declare that there are no conflicts of interest present.