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Effect of Modified Nucleotides on the Immunogenicity of the H1N1 Influenza mRNA Vaccine
S I Krasnikova1, S V Sharabrin2, D N Kisakov2
1State Research Center of Virology and Biotechnology "VECTOR", Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Koltsovo, Novosibirsk region, Russia. sveta.krasnikova2000@yandex.ru.
Abstract:
We analyzed the effect of modified nucleotides on the immunogenicity of mRNA vaccine encoding hemagglutinin of the influenza A/California/04/09(H1N1) pdm09 virus. Seven mRNA-H1 variants including the following modified bases in different ratios were obtained: N1-methylpseudouridine (m1Ψ), pseudouridine (Ψ), N6-methyladenine (m6A), and 5-methylcytidine (m5C). The efficacy of the resulting mRNA vaccines was assessed by their ability to induce specific antibodies and T-cell response in immunized mice. Virus-neutralizing activity was recorded in groups of animals immunized with mRNAs containing 100% m1Ψ, 100% Ψ, and 100% U. It was shown that mRNAs including 100% m1Ψ or 100% Ψ were more effective than other mRNA variants and induced potent B- and T-cell immune response.
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