Study of the safety and immunogenicity of VLP-based vaccine for the prevention of rotavirus infection in neonatal minipig model

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Introduction. In Russia, almost half of the cases of acute intestinal infections of established etiology in 2022 are due to rotavirus infection (RVI). There is no specific treatment for rotavirus gastroenteritis. There is a need to develop modern, effective and safe vaccines to combat rotavirus infection that are not capable of multiplying (replicating) in the body of the vaccinated person. A promising approach is to create vaccines based on virus-like particles (VLPs).

Objective. Study of the safety and immunogenicity of a vaccine against rotavirus infection based on virus-like particles of human rotavirus A in newborn minipigs with multiple intramuscular administration.

Materials and methods. Newborn minipigs were used as an animal model in this study. The safety of the tested vaccine was assessed based on thermometry data, clinical examination, body weight gain, clinical and biochemical blood parameters, as well as necropsy and histological examination. When studying the immunogenic properties of the Gam-VLP-rota vaccine in doses of 30 and 120 µg, the cellular, humoral and secretory immune response was studied.

Results. The results of assessing the general condition of animals during the immunization period, data from clinical, laboratory and pathomorphological studies indicate the safety of the vaccine against human rotavirus infection based on VLP (Gam-VLP-rota) when administered three times intramuscularly. Good local tolerance of the tested vaccine was demonstrated. The results of the assessment of humoral immunity indicate the formation of a stable immune response after three-time immunization with Gam-VLP-rota, stimulation of the production of antigen-specific IgG antibodies and their functional activity to neutralize human rotavirus A. It was shown that following the triple immunization with the minimum tested concentration of 30 µg/dose, animals developed a cell-mediated immune response. The results of the IgA titer in blood serum and intestinal lavages indicate the formation of both a systemic immunological response and the formation of specific secretory immunity to human rotavirus A.

Conclusion. Thus, three-time intramuscular immunization of minipigs with the Gam-VLP-rota vaccine forms stable protective humoral and cellular immunity in experimental animals. Evaluated vaccine is safe and has good local tolerability.

作者简介

Ludmila Kostina

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

编辑信件的主要联系方式.
Email: lvkostina@mail.ru
ORCID iD: 0000-0002-9556-1454

PhD, Senior Researcher at the Laboratory of Molecular Diagnostics, National Research Center for Epidemiology and Microbiology

俄罗斯联邦, 123098, Moscow

Ilya Filatov

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: filat69rus@yandex.ru
ORCID iD: 0000-0001-5274-224X

Junior Researcher, Laboratory of Molecular Diagnostics

俄罗斯联邦, 123098, Moscow

Olesya Eliseeva

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: olesenka80@mail.ru
ORCID iD: 0000-0002-0723-9749

PhD, Senior Researcher at the Laboratory of Molecular Diagnostics

俄罗斯联邦, 123098, Moscow

Oleg Latyshev

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: oleglat80@mail.ru
ORCID iD: 0000-0002-5757-3809

PhD, Head Laboratory of Immunology

俄罗斯联邦, 123098, Moscow

Yana Chernoryzh

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: revengeful_w@mail.ru
ORCID iD: 0000-0001-9848-8515

PhD, Researcher

俄罗斯联邦, 123098, Moscow

Kirill Yurlov

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: kir34292@yandex.ru
ORCID iD: 0000-0002-4694-2445

Researcher

俄罗斯联邦, 123098, Moscow

Ekaterina Lesnova

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: wolf252006@yandex.ru
ORCID iD: 0000-0002-2801-6843

Researcher

俄罗斯联邦, 123098, Moscow

Kizkhalum Khametova

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: kizkhalum@yandex.ru
ORCID iD: 0000-0002-8461-600X

PhD, Researcher

俄罗斯联邦, 123098, Moscow

Stanislav Cherepushkin

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: cherepushkin1@gmail.com
ORCID iD: 0000-0002-1734-5369

Researcher at the Laboratory of Molecular Diagnostics

俄罗斯联邦, 123098, Moscow

Tatyana Savochkina

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: tasavochkina@yandex.ru
ORCID iD: 0000-0003-4366-8476

Researcher, Laboratory of Molecular Diagnostics

俄罗斯联邦, 123098, Moscow

Valery Tsibezov

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: tsibezov@yandex.ru
ORCID iD: 0000-0003-2150-5764

PhD, Leading Researcher, Laboratory of Specific Prevention Products

俄罗斯联邦, 123098, Moscow

Kirill Kryshen

RMC «HOME OF PHARMACY» JSC

Email: kryshen.kl@doclinika.ru
ORCID iD: 0000-0003-1451-7716

PhD, head of specific toxicity and microbiology department

俄罗斯联邦, 188663, St. Petersburg

Liubov Alekseeva

RMC «HOME OF PHARMACY» JSC

Email: alekseeva.li@doclinika.ru
ORCID iD: 0000-0002-6510-9897

Junior Researcher, Department of Specific Toxicology and Pharmacodynamics, study director

俄罗斯联邦, 188663, St. Petersburg

Olga Zaykova

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: zaykova_o_n@mail.ru
ORCID iD: 0000-0003-4708-2069

PhD, senior researcher, Laboratory of Molecular Diagnostics, researcher in Diagnostic and Prevention

俄罗斯联邦, 123098, Moscow

Tatyana Grebennikova

National Research Center for Epidemiology and Microbiology named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation

Email: t_grebennikova@mail.ru
ORCID iD: 0000-0002-6141-9361

Dr Sci. (Biol.), Professor, Corresponding Member RAS, Head Laboratory of Molecular Diagnostics Head of the Testing Center, Deputy Director for Science

俄罗斯联邦, 123098, Moscow

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版权所有 © Kostina L.V., Filatov I.E., Eliseeva O.V., Latyshev O.E., Chernoryzh Y.Y., Yurlov K.I., Lesnova E.I., Khametova K.M., Cherepushkin S.A., Savochkina T.E., Tsibezov V.V., Kryshen K.L., Alekseeva L.I., Zaykova O.N., Grebennikova T.V., 2023

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