Rational optimization of glycoprotein E (gE)-encoding mRNA for improved Varicella-zoster virus mRNA vaccine
Lulu Huang1,2, Shun Zhang3, Tongyi Zhao1,2
1Vaccine Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People's Republic of China.
Emerging Microbes & Infections
|August 13, 2024
Summary
This study optimized a Varicella-zoster Virus (VZV) mRNA vaccine for enhanced immunogenicity. The novel VZV mRNA vaccine demonstrated superior antibody and T-cell responses across various mouse models.
Area of Science:
- Vaccinology
- Immunology
- Molecular Biology
Background:
- The Varicella-zoster Virus (VZV) mRNA vaccine platform shows potential for next-generation vaccine development.
- Current VZV vaccines aim to elicit robust T-cell responses, crucial for viral clearance.
Purpose of the Study:
- To optimize the VZV mRNA vaccine sequence for improved immunogenicity.
- To evaluate the efficacy of the enhanced VZV mRNA vaccine in preclinical models.
Main Methods:
- A combinatorial strategy was employed to optimize the gE-antigen-encoding mRNA sequence.
- Modifications included signal peptide replacement, C-terminal alterations, and the addition of mRNA-stabilizing motifs.
- The optimized vaccine's immunogenicity was assessed in adult, aged, and immunocompromised mice.
Main Results:
- The optimized VZV mRNA vaccine significantly enhanced vaccine immunogenicity compared to the first-generation vaccine.
- Superior induction of gE-specific antibodies and memory B-cell responses was observed.
- A strong Th1-type T-cell response was also elicited by the optimized vaccine.
Conclusions:
- The novel combinatorial strategy effectively improved the immunogenicity of the VZV mRNA vaccine.
- This optimized VZV mRNA vaccine holds promise for effective VZV prevention, particularly in vulnerable populations.
- Further development of this enhanced mRNA vaccine platform is warranted.
