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Abstract <p><b>Objective:</b> Influenza remains a serious global health threat due to viral variability and limitations of current vaccines. This study developed an mRNA vaccine encoding three influenza A virus antigens: hemagglutinin (HA), nucleoprotein (NP), and matrix protein (M1). <b>Methods:</b> The mRNA was encapsulated in liposomes for efficient delivery. Mice received two immunizations: one group received HA alone (30 μg), while the other received a combination of HA + NP + M1 (10 μg each). Electron microscopy was used to confirm the formation of virus-like particles (VLPs). <b>Results and Discussion:</b> The trivalent vaccine induced higher antibody titers (geometric mean titer 4677 vs 3243) compared to the monovalent HA vaccine. Electron microscopy confirmed the formation of VLPs upon co-expression of HA, NP and M1, which enhanced immune responses. Against heterologous A/WSN/1933 (H1N1) challenge, the trivalent vaccine provided 83% survival, compared to only 50% with the monovalent vaccine. <b>Conclusions:</b> These results demonstrate the promise of VLP-based mRNA vaccines for protection against diverse influenza strains.</p>

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Co-Administration of mRNAs Encoding HA, M1, and NP Antigens of the Influenza Virus Leads to the Formation of Virus-Like Particles and an Enhanced Immune Response

  • 期刊论文

  • 发表日期：

    2026年7月2日

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  • O. V. Markov,
  • M. V. Sergeeva,
  • D. N. Shcherbakov,
  • D. N. Antropov,
  • E. P. Goncharova,
  • E. S. Zhuravlev,
  • A. S. Dome,
  • A. S. Fomin,
  • S. I. Gayvoronsky,
  • K. S. Kudrya,
  • A. A. Isaeva,
  • E. A. Volosnikova,
  • A. V. Chechushkov,
  • E. V. Shmendel,
  • P. A. Puchkov,
  • Y. E. Poletaeva,
  • E. S. Ryabova,
  • M. A. Maslov,
  • V. V. Koval,
  • G. A. Stepanov

摘要

Abstract

Objective: Influenza remains a serious global health threat due to viral variability and limitations of current vaccines. This study developed an mRNA vaccine encoding three influenza A virus antigens: hemagglutinin (HA), nucleoprotein (NP), and matrix protein (M1). Methods: The mRNA was encapsulated in liposomes for efficient delivery. Mice received two immunizations: one group received HA alone (30 μg), while the other received a combination of HA + NP + M1 (10 μg each). Electron microscopy was used to confirm the formation of virus-like particles (VLPs). Results and Discussion: The trivalent vaccine induced higher antibody titers (geometric mean titer 4677 vs 3243) compared to the monovalent HA vaccine. Electron microscopy confirmed the formation of VLPs upon co-expression of HA, NP and M1, which enhanced immune responses. Against heterologous A/WSN/1933 (H1N1) challenge, the trivalent vaccine provided 83% survival, compared to only 50% with the monovalent vaccine. Conclusions: These results demonstrate the promise of VLP-based mRNA vaccines for protection against diverse influenza strains.