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

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.