<p>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.</p>

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Effect of Modified Nucleotides on the Immunogenicity of the H1N1 Influenza mRNA Vaccine

  • S. I. Krasnikova,
  • S. V. Sharabrin,
  • D. N. Kisakov,
  • M. B. Borgoyakova,
  • E. V. Starostina,
  • E. V. Tigeeva,
  • K. P. Makarova,
  • V. A. Yakovlev,
  • K. I. Ivanova,
  • A. P. Rudometov,
  • A. A. Ilyichev,
  • L. I. Karpenko

摘要

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.