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

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.

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Publication Details

Journal
npj Vaccines
Published
2025-11-24
DOI
https://doi.org/10.1038/s41541-025-01298-4
Primary Topic
Viral Infections and Vectors
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Andrew M. Ryder, Nam-Hyuk Cho, Chih‐Jen Lai, Myles Lewis et al.
npj Vaccines
Viral Infections and Vectors
article

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

Andrew M. Ryder, Nam-Hyuk Cho, Chih‐Jen Lai, Myles Lewis, Young Ki Choi, Chong Hyuk Chung, Jae U. Jung, Woo-Jin Shin, Yumiko Yamada, In–Ho Cha, Soowon Kang, Wan-Shan Yang, Jiànróng Lǐ, Do-Kyun Kim
article en

Abstract

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.

npj VaccinesVol. 10(1)
Cleveland Clinic (US), Seoul National University (KR), National Sun Yat-sen University (TW), Institute for Basic Science (KR), University School (US), The Ohio State University (US), Case Western Reserve University (US)
Cleveland Clinic, National Science and Technology Council, National Institutes of Health
Openalex Percentile: Top 58%
Viral Infections and Vectors
DOIOpen Access PDFOpenAlex
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