Ferritin-binding and ubiquitination-modified mRNA vaccines induce potent immune responses and protective efficacy against SARS-CoV-2

文献类型： 外文期刊

第一作者： Yu, Tong

作者： Yu, Tong;Xing, Junhong;Yu, Tong;Yang, Songhui;Zhuang, Xinyu;Jin, Ningyi;Tian, Mingyao;Zhang, Tong;Zhang, Chenchao;Xu, Zhiqiang;Jiang, Renyue;Tang, Jiafeng;Di, Yaxin

作者机构：

关键词： SARS-CoV-2; mRNA vaccines; Ubiquitination modification; Inflammatory cytokine

期刊名称：INTERNATIONAL IMMUNOPHARMACOLOGY （ 影响因子：5.6； 五年影响因子：5.6 ）

ISSN： 1567-5769

年卷期： 2024 年 129 卷

页码：

收录情况： SCI

摘要： Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) incessantly engenders mutating strains via immune escape mechanisms, substantially escalating the risk of severe acute respiratory syndrome. In this context, the urgent development of innovative and efficacious mRNA vaccines is imperative. In our study, we synthesized six unique mRNA vaccine formulations: the Receptor Binding Domain (RBD) monomer vaccine, RBD dimer (2RBD) vaccine, RBD-Ferritin (RBD-Fe) vaccine, ubiquitin-modified wild-type Nucleocapsid gene (WT-N) vaccine, rearranged Nucleocapsid gene (Re-N) vaccine, and an epitope-based (COVID-19 epitope) vaccine, all encapsulated within the lipid nanoparticle SM102. Immunization studies conducted on C57BL/6 mice with these vaccines revealed that the RBD monomer, RBD dimer (2RBD), and RBD-Fe vaccines elicited robust titers of specific antibodies, including neutralizing antibodies. In contrast, the wild-type N gene (WT-N), rearrange N gene (Re-N), and COVID-19 epitope vaccines predominantly induced potent cellular immune responses. Protective efficacy assays in golden hamsters demonstrated that vaccinated cohorts showed significant reduction in lung pathology, markedly lower viral loads in the lungs, nasal turbinates, and trachea, and substantially reduced transcriptional and expression levels of pro-inflammatory cytokines. Overall, our vaccine candidates pave the way for novel strategies in vaccine development against various infectious agents and establish a critical foundation for the formulation of advanced vaccines targeting emerging pathogens.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序