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Article

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

1
State Research Center of Virology and Biotechnology “Vector”, Koltsovo, 630559 Novosibirsk, Russia
2
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
3
Institute of Molecular and Cellular Biology, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
*
Author to whom correspondence should be addressed.
Alexander A. Ilyichev and Larisa I. Karpenko are co-last authors.
Academic Editors: Maria G. Isaguliants and Felicity Jane Burt
Vaccines 2021, 9(5), 452; https://doi.org/10.3390/vaccines9050452
Received: 10 March 2021 / Revised: 15 April 2021 / Accepted: 29 April 2021 / Published: 3 May 2021
(This article belongs to the Special Issue Perspective Technologies of Vaccination and Immunotherapy)
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. View Full-Text
Keywords: mRNA-vaccine; influenza virus; mRNA modification; Anti-Reverse Cap Analog; pseudouridine; N6-methyladenosine; 5-methylcytosine mRNA-vaccine; influenza virus; mRNA modification; Anti-Reverse Cap Analog; pseudouridine; N6-methyladenosine; 5-methylcytosine
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MDPI and ACS Style

Starostina, E.V.; Sharabrin, S.V.; Antropov, D.N.; Stepanov, G.A.; Shevelev, G.Y.; Lemza, A.E.; Rudometov, A.P.; Borgoyakova, M.B.; Rudometova, N.B.; Marchenko, V.Y.; Danilchenko, N.V.; Chikaev, A.N.; Bazhan, S.I.; Ilyichev, A.A.; Karpenko, L.I. Construction and Immunogenicity of Modified mRNA-Vaccine Variants Encoding Influenza Virus Antigens. Vaccines 2021, 9, 452. https://doi.org/10.3390/vaccines9050452

AMA Style

Starostina EV, Sharabrin SV, Antropov DN, Stepanov GA, Shevelev GY, Lemza AE, Rudometov AP, Borgoyakova MB, Rudometova NB, Marchenko VY, Danilchenko NV, Chikaev AN, Bazhan SI, Ilyichev AA, Karpenko LI. Construction and Immunogenicity of Modified mRNA-Vaccine Variants Encoding Influenza Virus Antigens. Vaccines. 2021; 9(5):452. https://doi.org/10.3390/vaccines9050452

Chicago/Turabian Style

Starostina, Ekaterina V., Sergei V. Sharabrin, Denis N. Antropov, Grigory A. Stepanov, Georgiy Y. Shevelev, Anna E. Lemza, Andrey P. Rudometov, Mariya B. Borgoyakova, Nadezhda B. Rudometova, Vasiliy Y. Marchenko, Natalia V. Danilchenko, Anton N. Chikaev, Sergei I. Bazhan, Alexander A. Ilyichev, and Larisa I. Karpenko. 2021. "Construction and Immunogenicity of Modified mRNA-Vaccine Variants Encoding Influenza Virus Antigens" Vaccines 9, no. 5: 452. https://doi.org/10.3390/vaccines9050452

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