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<p>Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) is an emerging tick-borne pathogen with a high case-fatality rate and no approved vaccine, posing a global health threat. Human codon-optimized viral antigens can enhance mRNA vaccine efficacy by improving antigen expression but often requires high mRNA doses, increasing the risk of side effects. In this study, we introduce a codon optimization strategy using Herpes Simplex Virus 1 glycoprotein B (HSVgB) codon usage to develop an mRNA lipid nanoparticle (LNP) vaccine targeting the neutralizing Gn-H domain of SFTSV (sGn-H). The HSVgB codon-optimized mRNA vaccine [sGn-H (HSVgB)] achieved higher antigen expression and elicited stronger humoral and cellular immune responses than a human codon-optimized counterpart [sGn-H (human)]. Notably, sGn-H (HSVgB) induced more bone marrow-resident antibody-secreting cells and conferred superior protection against SFTSV at lower doses. These findings highlight HSVgB codon optimization may represent a promising strategy for enhancing the immunogenicity with low-dose mRNA immunization.</p>

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A viral codon usage strategy enhances antigen production and protection in SFTSV mRNA vaccination

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月24日

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  • Inho Cha,
  • Yumiko Yamada,
  • Dokyun Kim,
  • Soowon Kang,
  • Wan-Shan Yang,
  • Woo-Jin Shin,
  • Anna Ryder,
  • Morgan Lewis,
  • Chloe Chung,
  • Nam-Hyuk Cho,
  • Young Ki Choi,
  • Jianrong Li,
  • Chih-Jen Lai,
  • Jae U. Jung

摘要

Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) is an emerging tick-borne pathogen with a high case-fatality rate and no approved vaccine, posing a global health threat. Human codon-optimized viral antigens can enhance mRNA vaccine efficacy by improving antigen expression but often requires high mRNA doses, increasing the risk of side effects. In this study, we introduce a codon optimization strategy using Herpes Simplex Virus 1 glycoprotein B (HSVgB) codon usage to develop an mRNA lipid nanoparticle (LNP) vaccine targeting the neutralizing Gn-H domain of SFTSV (sGn-H). The HSVgB codon-optimized mRNA vaccine [sGn-H (HSVgB)] achieved higher antigen expression and elicited stronger humoral and cellular immune responses than a human codon-optimized counterpart [sGn-H (human)]. Notably, sGn-H (HSVgB) induced more bone marrow-resident antibody-secreting cells and conferred superior protection against SFTSV at lower doses. These findings highlight HSVgB codon optimization may represent a promising strategy for enhancing the immunogenicity with low-dose mRNA immunization.