COVID-19.рф: ИНФОРМАЦИЯ ПРОТИВ ПАНДЕМИИ

Поиск по репозиторию

Статья

Construction and Immunogenicity of Modified mRNA-Vaccine Variants Encoding Influenza Virus Antigens

E. Starostina, S. Sharabrin, D. Antropov, G. Stepanov, G. Shevelev, A. Lemza, A. Rudometov, M. Borgoyakova, N. Rudometova, V. Marchenko, N. Danilchenko, A. Chikaev, S. Bazhan, A. Ilyichev, L. Karpenko,
2021
https://doi.org/10.3390/vaccines9050452

Nucleic acid-based influenza vaccines are a promising platform that have recently and rapidly developed. We previously demonstrated the immunogenicity of DNA vaccines encoding artificial immunogens AgH1, AgH3, and AgM2, which contained conserved fragments of the hemagglutinin stem of two subtypes of influenza A-H1N1 and H3N2-and conserved protein M2. Thus, the aim of this study was to design and characterize modified mRNA obtained using the above plasmid DNA vaccines as a template. To select the most promising protocol for creating highly immunogenic mRNA vaccines, we performed a comparative analysis of mRNA modifications aimed at increasing its translational activity and decreasing toxicity. We used mRNA encoding a green fluorescent protein (GFP) as a model. Eight mRNA-GFP variants with different modifications (M0-M7) were obtained using the classic cap(1), its chemical analog ARCA (anti-reverse cap analog), pseudouridine (Ψ), N6-methyladenosine (m6A), and 5-methylcytosine (m5C) in different ratios. Modifications M2, M6, and M7, which provided the most intensive fluorescence of transfected HEK293FT cells were used for template synthesis when mRNA encoded influenza immunogens AgH1, AgH3, and AgM2. Virus specific antibodies were registered in groups of animals immunized with a mix of mRNAs encoding AgH1, AgH3, and AgM2, which contained either ARCA (with inclusions of 100% Ψ and 20% m6A (M6)) or a classic cap(1) (with 100% substitution of U with Ψ (M7)). M6 modification was the least toxic when compared with other mRNA variants. M6 and M7 RNA modifications can therefore be considered as promising protocols for designing mRNA vaccines.

Цитирование

Похожие публикации

Construction and immunogenicity of a novel multivalent vaccine prototype based on conserved influenza virus antigens
A. Kirsteina, I. Akopjana, J. Bogans,
In silico design of influenza a virus artificial epitope-based T-cell antigens and the evaluation of their immunogenicity in mice
S. Bazhan, D. Antonets, E. Starostina,
Various Adjuvants Effect on Immunogenicity of Puumala Virus Vaccine
S. Kurashova, A. Ishmukhametov, T. Dzagurova,

Версии

  • 1. Version of Record от 2021-05-03

Метаданные

Об авторах
  • E. Starostina
    State Research Center of Virology and Biotechnology “Vector”, Koltsovo, 630559 Novosibirsk, Russia;, sharabrin.sv@gmail.com, (S.V.S.);, rudometov_ap@vector.nsc.ru, (A.P.R.);, borgoyakova_mb@vector.nsc.ru, (M.B.B.);, andreeva_nb@vector.nsc.ru, (N.B.R.);, marchenko_vyu@vector.nsc.ru, (V.Y.M.);, danilchenko_nv@vector.nsc.ru, (N.V.D.);, bazhan@vector.nsc.ru, (S.I.B.);, ilyichev@vector.nsc.ru, (A.A.I.);, lkarpenko@ngs.ru, (L.I.K.)
  • S. Sharabrin
    State Research Center of Virology and Biotechnology “Vector”, Koltsovo, 630559 Novosibirsk, Russia;, sharabrin.sv@gmail.com, (S.V.S.);, rudometov_ap@vector.nsc.ru, (A.P.R.);, borgoyakova_mb@vector.nsc.ru, (M.B.B.);, andreeva_nb@vector.nsc.ru, (N.B.R.);, marchenko_vyu@vector.nsc.ru, (V.Y.M.);, danilchenko_nv@vector.nsc.ru, (N.V.D.);, bazhan@vector.nsc.ru, (S.I.B.);, ilyichev@vector.nsc.ru, (A.A.I.);, lkarpenko@ngs.ru, (L.I.K.)
  • D. Antropov
    Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia;, antr0povdn@yandex.ru, (D.N.A.);, stepanovga@niboch.nsc.ru, (G.A.S.);, metatezis@gmail.com, (G.Y.S.);, lemza.ae@yandex.ru, (A.E.L.)
  • G. Stepanov
    Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia;, antr0povdn@yandex.ru, (D.N.A.);, stepanovga@niboch.nsc.ru, (G.A.S.);, metatezis@gmail.com, (G.Y.S.);, lemza.ae@yandex.ru, (A.E.L.)
  • G. Shevelev
    Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia;, antr0povdn@yandex.ru, (D.N.A.);, stepanovga@niboch.nsc.ru, (G.A.S.);, metatezis@gmail.com, (G.Y.S.);, lemza.ae@yandex.ru, (A.E.L.)
  • A. Lemza
    Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia;, antr0povdn@yandex.ru, (D.N.A.);, stepanovga@niboch.nsc.ru, (G.A.S.);, metatezis@gmail.com, (G.Y.S.);, lemza.ae@yandex.ru, (A.E.L.)
  • A. Rudometov
    State Research Center of Virology and Biotechnology “Vector”, Koltsovo, 630559 Novosibirsk, Russia;, sharabrin.sv@gmail.com, (S.V.S.);, rudometov_ap@vector.nsc.ru, (A.P.R.);, borgoyakova_mb@vector.nsc.ru, (M.B.B.);, andreeva_nb@vector.nsc.ru, (N.B.R.);, marchenko_vyu@vector.nsc.ru, (V.Y.M.);, danilchenko_nv@vector.nsc.ru, (N.V.D.);, bazhan@vector.nsc.ru, (S.I.B.);, ilyichev@vector.nsc.ru, (A.A.I.);, lkarpenko@ngs.ru, (L.I.K.)
  • M. Borgoyakova
    State Research Center of Virology and Biotechnology “Vector”, Koltsovo, 630559 Novosibirsk, Russia;, sharabrin.sv@gmail.com, (S.V.S.);, rudometov_ap@vector.nsc.ru, (A.P.R.);, borgoyakova_mb@vector.nsc.ru, (M.B.B.);, andreeva_nb@vector.nsc.ru, (N.B.R.);, marchenko_vyu@vector.nsc.ru, (V.Y.M.);, danilchenko_nv@vector.nsc.ru, (N.V.D.);, bazhan@vector.nsc.ru, (S.I.B.);, ilyichev@vector.nsc.ru, (A.A.I.);, lkarpenko@ngs.ru, (L.I.K.)
  • N. Rudometova
    State Research Center of Virology and Biotechnology “Vector”, Koltsovo, 630559 Novosibirsk, Russia;, sharabrin.sv@gmail.com, (S.V.S.);, rudometov_ap@vector.nsc.ru, (A.P.R.);, borgoyakova_mb@vector.nsc.ru, (M.B.B.);, andreeva_nb@vector.nsc.ru, (N.B.R.);, marchenko_vyu@vector.nsc.ru, (V.Y.M.);, danilchenko_nv@vector.nsc.ru, (N.V.D.);, bazhan@vector.nsc.ru, (S.I.B.);, ilyichev@vector.nsc.ru, (A.A.I.);, lkarpenko@ngs.ru, (L.I.K.)
  • V. Marchenko
    State Research Center of Virology and Biotechnology “Vector”, Koltsovo, 630559 Novosibirsk, Russia;, sharabrin.sv@gmail.com, (S.V.S.);, rudometov_ap@vector.nsc.ru, (A.P.R.);, borgoyakova_mb@vector.nsc.ru, (M.B.B.);, andreeva_nb@vector.nsc.ru, (N.B.R.);, marchenko_vyu@vector.nsc.ru, (V.Y.M.);, danilchenko_nv@vector.nsc.ru, (N.V.D.);, bazhan@vector.nsc.ru, (S.I.B.);, ilyichev@vector.nsc.ru, (A.A.I.);, lkarpenko@ngs.ru, (L.I.K.)
  • N. Danilchenko
    State Research Center of Virology and Biotechnology “Vector”, Koltsovo, 630559 Novosibirsk, Russia;, sharabrin.sv@gmail.com, (S.V.S.);, rudometov_ap@vector.nsc.ru, (A.P.R.);, borgoyakova_mb@vector.nsc.ru, (M.B.B.);, andreeva_nb@vector.nsc.ru, (N.B.R.);, marchenko_vyu@vector.nsc.ru, (V.Y.M.);, danilchenko_nv@vector.nsc.ru, (N.V.D.);, bazhan@vector.nsc.ru, (S.I.B.);, ilyichev@vector.nsc.ru, (A.A.I.);, lkarpenko@ngs.ru, (L.I.K.)
  • A. Chikaev
    Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia;, chikaev@mcb.nsc.ru
  • S. Bazhan
    State Research Center of Virology and Biotechnology “Vector”, Koltsovo, 630559 Novosibirsk, Russia;, sharabrin.sv@gmail.com, (S.V.S.);, rudometov_ap@vector.nsc.ru, (A.P.R.);, borgoyakova_mb@vector.nsc.ru, (M.B.B.);, andreeva_nb@vector.nsc.ru, (N.B.R.);, marchenko_vyu@vector.nsc.ru, (V.Y.M.);, danilchenko_nv@vector.nsc.ru, (N.V.D.);, bazhan@vector.nsc.ru, (S.I.B.);, ilyichev@vector.nsc.ru, (A.A.I.);, lkarpenko@ngs.ru, (L.I.K.)
  • A. Ilyichev
    State Research Center of Virology and Biotechnology “Vector”, Koltsovo, 630559 Novosibirsk, Russia;, sharabrin.sv@gmail.com, (S.V.S.);, rudometov_ap@vector.nsc.ru, (A.P.R.);, borgoyakova_mb@vector.nsc.ru, (M.B.B.);, andreeva_nb@vector.nsc.ru, (N.B.R.);, marchenko_vyu@vector.nsc.ru, (V.Y.M.);, danilchenko_nv@vector.nsc.ru, (N.V.D.);, bazhan@vector.nsc.ru, (S.I.B.);, ilyichev@vector.nsc.ru, (A.A.I.);, lkarpenko@ngs.ru, (L.I.K.)
  • L. Karpenko
    State Research Center of Virology and Biotechnology “Vector”, Koltsovo, 630559 Novosibirsk, Russia;, sharabrin.sv@gmail.com, (S.V.S.);, rudometov_ap@vector.nsc.ru, (A.P.R.);, borgoyakova_mb@vector.nsc.ru, (M.B.B.);, andreeva_nb@vector.nsc.ru, (N.B.R.);, marchenko_vyu@vector.nsc.ru, (V.Y.M.);, danilchenko_nv@vector.nsc.ru, (N.V.D.);, bazhan@vector.nsc.ru, (S.I.B.);, ilyichev@vector.nsc.ru, (A.A.I.);, lkarpenko@ngs.ru, (L.I.K.)
Название журнала
  • Vaccines
Том
  • 9
Выпуск
  • 5
Страницы
  • 452
Издатель
  • MDPI
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC BY
Правовой статус документа
  • Свободная лицензия
Источник
  • dimensions
COVID-19.рф: Информация против пандемии

Адрес: 115114, Москва, ул. Летниковская, д. 4, стр.5, офис 2.4
тел.\факс: +7(499)754-99-94, доб. 502
e-mail: covid19@neicon.ru

Проект реализуется с использованием гранта Президента Российской Федерации на развитие гражданского общества, предоставленного Фондом президентских грантов.

Содержимое сайта, если не указано иное, опубликовано в соответствии с лицензией Creative Commons «Attribution» («Атрибуция») 4.0 Всемирная (CC BY 4.0). Права на материалы, переданные партнерами проекта, принадлежат их правообладателям.

© 2025 NEICON