Multivariate analysis of the parameters of the immune response after immunization with inactivated influenza vaccines

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Abstract

Influenza A and B viruses are widely spread respiratory pathogens of humans and cause both isolated cases and local outbreaks of the disease, as well as massive seasonal epidemics and pandemics. Vaccination is the main strategy for combating influenza, and an increase in the proportion of vaccinated people in the population determines the success of vaccination. To identify patterns of postvaccination immune response formation to different types of vaccines and assess the significance of its multiple parameters the appropriate statistical methods should by applied. These methods allow to operate with large datasets and reduce their dimension, while keeping the maximum of information about the differences between individual observations. The aim of our study was the analysis of parameters of humoral and cellular immunity and their dynamics after vaccination with different types of inactivated influenza vaccines (IIV) using statistical methods of complex data analysis. The study was conducted in the clinical department of the Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, in the flu season 2018 – 2019. The multivariate analysis of the immune response parameters after immunization with IIV “Grippol plus”, “Sovigripp” “Ultrix” included data obtained for 39 volunteers before vaccination, on the 7th and 21st days after vaccination. To identify parameters with significant differences between groups, one-factor analysis of variance (ANOVA) was used separately for each parameter and time point. To visualize the differences in the parameters selected in the analysis of variance, the Principal component analysis (PCA) method was used. The conducted studies revealed the peculiarities of the formation of a post-vaccination immune response to various types of IIV. It was shown that the factors of antigen-specific CD4+ and CD8+ T-cell immune response introduced the major contribution to the formation of the differences between groups. The approach is a powerful tool in analyzing the parameters of the immune response in clinical trials of influenza vaccines and other preventive medicine.

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About the authors

K. A. Vasiliev

Federal State Budgetary Institution «Research Institute of Influenza A.A. Smorodintsev» of the Ministry of Health of Russia

Email: cytokines@yandex.ru

candidate of biological sciences, researcher
Russian Federation, 197376, Prof. Popov str., 15/17, St. Petersburg

A.-P. S. Shurygina

Federal State Budgetary Institution «Research Institute of Influenza A.A. Smorodintsev» of the Ministry of Health of Russia

Email: cytokines@yandex.ru

candidate of medical sciences, senior researcher

Russian Federation, 197376, Prof. Popov str., 15/17, St. Petersburg

M. V. Sergeeva

Federal State Budgetary Institution «Research Institute of Influenza A.A. Smorodintsev» of the Ministry of Health of Russia

Email: cytokines@yandex.ru

leading researcher, candidate of biological sciences

Russian Federation, 197376, Prof. Popov str., 15/17, St. Petersburg

E. A. Romanovskaya-Romanko

Federal State Budgetary Institution «Research Institute of Influenza A.A. Smorodintsev» of the Ministry of Health of Russia

Email: cytokines@yandex.ru

senior researcher, candidate of biological sciences

Russian Federation, 197376, Prof. Popov str., 15/17, St. Petersburg

V. Z. Krivitskaya

Federal State Budgetary Institution «Research Institute of Influenza A.A. Smorodintsev» of the Ministry of Health of Russia

Email: cytokines@yandex.ru

leading researcher of the laboratory for the study of risk factors for influenza and SARS, doctor of biological sciences

Russian Federation, 197376, Prof. Popov str., 15/17, St. Petersburg

I. V. Amosova

Federal State Budgetary Institution «Research Institute of Influenza A.A. Smorodintsev» of the Ministry of Health of Russia

Email: cytokines@yandex.ru

head of the laboratory of cell cultures, candidate of biological sciences

Russian Federation, 197376, Prof. Popov str., 15/17, St. Petersburg

E. A. Varyushina

Federal State Budgetary Institution «Research Institute of Influenza A.A. Smorodintsev» of the Ministry of Health of Russia

Author for correspondence.
Email: elena.varyushina@influenza.spb.ru

doctor of biological sciences, leading specialist in the field of laboratory research

Russian Federation, 197376, Prof. Popov str., 15/17, St. Petersburg

Z. V. Buzitskaya

Federal State Budgetary Institution «Research Institute of Influenza A.A. Smorodintsev» of the Ministry of Health of Russia

Email: cytokines@yandex.ru

candidate of biological sciences, leading researcher

Russian Federation, 197376, Prof. Popov str., 15/17, St. Petersburg

M. A. Stukova

Federal State Budgetary Institution «Research Institute of Influenza A.A. Smorodintsev» of the Ministry of Health of Russia

Email: cytokines@yandex.ru

candidate of medical sciences, head of the laboratory

Russian Federation, 197376, Prof. Popov str., 15/17, St. Petersburg

D. A. Lioznov

Federal State Budgetary Institution «Research Institute of Influenza A.A. Smorodintsev» of the Ministry of Health of Russia

Email: cytokines@yandex.ru

ddoctor of medical sciences, director of the institute

Russian Federation, 197376, Prof. Popov str., 15/17, St. Petersburg

References

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Supplementary files

Supplementary Files
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2. Рис. 1. Средняя кратность изменений параметров иммунного ответа, по которым наблюдали наиболее выраженные различия между исследуемыми группами на 7-й день после вакцинации. Цвет столбцов обо- значает специфичность параметра иммунного ответа к подтипу вируса гриппа А или B. Символами -++, -+-, +++ и т. д. обозначены популяции цитокин-продуцирующих CD4+ и CD8+ Т-лимфоцитов: IFNγ-IL2+TNFα+, IFNγ-IL2+TNFα-, IFNγ+IL2+TNFα- и т. д.)

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3. Рис. 2. Визуализация различий параметров иммунного ответа между группами при помощи метода главных компонент (PCA) на 7-й день после вакцинации. Применена «min-max» нормализация. Все данные расположены на шкале [-1;1] с сохранением исходных расстояний между точками. Цветными символами обозначены значения первых двух главных компонент у каждого участника исследования. Цвет точек обо- значает принадлежность соответствующих наблюдений к группам вакцин «Совигрипп», «Гриппол плюс» или «Ультрикс». Текстом на графике обозначены названия изучаемых параметров иммунного ответа. Символа- ми -++, -+-, +++ и т. д. обозначены популяции цитокин-продуцирующих CD4+ и CD8+ Т-лимфоцитов: IFNγ- IL2+TNFα+, IFNγ-IL2+TNFα-, IFNγ+IL2+TNFα- и т. д. Цвет текста обозначает специфичность того или иного па- раметра иммунного ответа к вирусам гриппа подтипа A или B. Пунктирные линии вокруг вершин векторов ограничивают кластеры переменных, характеризующихся близкими значениями факторных нагрузок на две первые главные компоненты

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4. Рис. 3. Средняя кратность изменений параметров иммунного ответа, по которым наблюдались наи- более выраженные различия между исследуемыми группами на 21-й день после вакцинации. Обозначения те же, что на рис. 1

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5. Рис. 4. Визуализация различий между группами при помощи метода главных компонент (PCA) на 21-й день после вакцинации. Обозначения те же, что на рис. 2

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Copyright (c) 2023 Vasiliev K.A., Shurygina A.S., Sergeeva M.V., Romanovskaya-Romanko E.A., Krivitskaya V.Z., Amosova I.V., Varyushina E.A., Buzitskaya Z.V., Stukova M.A., Lioznov D.A.

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