Rational optimization of glycoprotein E (gE)-encoding mRNA for improved Varicella-zoster virus mRNA vaccine development

mRNA platform holds promise for next-generation Varicella-zoster Virus (VZV) vaccine development due to its high potency at inducing strong T-cell response. Built upon the design of our 1st-generation VZV mRNA vaccine that encodes for full-length gE antigen, in this study we reported on a novel combinatorial strategy to further optimize the gE-encoding mRNA sequence through signal peptide replacement, C-terminal modification, and insertion of mRNA-stabilizing motif, which collectively contributed to significantly improved vaccine immunogenicity. In adult mice, aged mice, and immunocompromised mice, this optimized VZV mRNA vaccine showed strong superiority in multiple aspects including the induction of gE-specific antibodies, specific memory B-cell response, as well as Th1-type T-cell response.

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Publication Details

Journal
Emerging Microbes & Infections
Published
2024-08-13
DOI
https://doi.org/10.1080/22221751.2024.2392661
Citations
8
Primary Topic
Herpesvirus Infections and Treatments
Type
article
Field-Weighted Citation Impact
3.09

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article

Rational optimization of glycoprotein E (gE)-encoding mRNA for improved Varicella-zoster virus mRNA vaccine development

Ting Cai, Zhenhua Di, Ang Lin, Lingling Bu et al.
8 citations
Emerging Microbes & Infections
Herpesvirus Infections and Treatments
3.09
article

Rational optimization of glycoprotein E (gE)-encoding mRNA for improved Varicella-zoster virus mRNA vaccine development

Ting Cai, Zhenhua Di, Ang Lin, Lingling Bu, Tongyi Zhao, Yang Chen, Yong Yang, Lulu Huang, Shun Zhang, Yujie Zhang
article en
8 citations

Abstract

mRNA platform holds promise for next-generation Varicella-zoster Virus (VZV) vaccine development due to its high potency at inducing strong T-cell response. Built upon the design of our 1st-generation VZV mRNA vaccine that encodes for full-length gE antigen, in this study we reported on a novel combinatorial strategy to further optimize the gE-encoding mRNA sequence through signal peptide replacement, C-terminal modification, and insertion of mRNA-stabilizing motif, which collectively contributed to significantly improved vaccine immunogenicity. In adult mice, aged mice, and immunocompromised mice, this optimized VZV mRNA vaccine showed strong superiority in multiple aspects including the induction of gE-specific antibodies, specific memory B-cell response, as well as Th1-type T-cell response.

Emerging Microbes & InfectionsVol. 13(1)
Shandong University (CN), China Pharmaceutical University (CN), Xuzhou Medical College (CN), University of Chinese Academy of Sciences (CN)
National Science Foundation, National Natural Science Foundation of China, China Pharmaceutical University, Government of Jiangsu Province, Natural Science Foundation of Jiangsu Province, Fundamental Research Funds for the Central Universities
Zero hunger
Openalex Percentile: Top 8%
Herpesvirus Infections and Treatments
3.09
DOIOpen Access PDFOpenAlex
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