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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. 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