Needle-free jet-delivered mRNA-vaccine encoding influenza A(H1N1)PDM09 hemagglutinin protects mice from lethal virus infection.

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Abstract

Seasonal influenza is an acute respiratory illness caused by influenza A and B viruses that circulate worldwide. Due to high variability, new strains of the virus emerge every year. Therefore, vaccine formulation has to be revised every year. The advantages of mRNA vaccines are that they can be produced quickly, and without preliminary adaptation of the vaccine strain to chicken embryos. Here, the results of developing and studying the mRNA-C3-H1 vaccine encoding the hemagglutinin (HA) of the influenza A(H1N1)pdm09 virus are presented. The design and production of a DNA-template for the synthesis of mature HA mRNA in one step were described. The obtained mRNA was purified from double-stranded RNA impurities using a method based on the use of cellulose powder. The efficacy of the vaccine was assessed on BALB/c mice. The mice were immunized with “naked” mRNA vaccine using a needle-free jet injector. According to ELISA results, the average antibody titer in the serum of immunized animals was 4.6 × 105. Sera of immunized animals neutralized the mouse-adapted influenza A/California/04/09 (H1N1) MA8 virus with an average titer of 6 × 102. As shown by the ELISpot, the developed mRNA vaccine induced a T-cell immune response in mice. After stimulation of splenocytes with specific peptides, the average number of T-lymphocytes secreting IFN-γ was 236 per 106 cells. Immunization with the mRNA vaccine was shown to protect mice from infection with a lethal dose of the influenza A/California/04/09 (H1N1) MA8 virus. Thus, the developed experimental mRNA-C3-H1 vaccine is immunogenic and prevents morbidity and mortality in mice after infection with a homologous strain of influenza virus.

About the authors

S. V. Sharabrin

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

A. A. Ilyichev

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

D. N. Kisakov

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

M. B. Borgoyakova

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

E. V. Starostina

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

L. A. Kisakova

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

A. A. Isaeva

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

D. N. Shcherbakov

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

S. I. Krasnikova

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

A. S. Gudymo

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

K. I. Ivanova

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

V. Y. Marchenko

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

V. A. Yakovlev

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

E. V. Tigeeva

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

T. N. Ilyicheva

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

N. B. Rudometova

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

A. A. Fando

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

A. P. Rudometov

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

A. A. Sergeev

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

L. I. Karpenko

Federal Budgetary Research Institution State Research Center of Virology and Biotechnology “Vector”, Rospotrebnadzor

Author for correspondence.
Email: Sharabrin.sv@gmail.com
Russian Federation, Koltsovo, Novosibirsk Region, 630559

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Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».