Exosome-based delivery of VP1 protein conferred enhanced resistance of mice to CVB3-induced viral myocarditis.
Exosome-based delivery of VP1 protein conferred enhanced resistance of mice to CVB3-induced viral myocarditis.
复制标题
DOI：
10.1016/j.virol.2022.12.015
复制
发表时间：
2023-01
期刊：
影响因子：
3.7
通讯作者：
Changwei Zhang;Yu Zhang;Yuanyuan Li;Juan Lu;S. Xiong;Y. Yue
中科院分区：
文献类型：
--
作者：
Changwei Zhang;Yu Zhang;Yuanyuan Li;Juan Lu;S. Xiong;Y. Yue
柯萨奇病毒B3（CVB3）是病毒性心肌炎的重要病因，临床上尚无疫苗可用。在此，我们构建了一种基于外泌体的抗CVB3疫苗（Exo-VP1），并将其免疫原性和免疫保护性与我们之前报道的重组VP1蛋白（rVP1）疫苗进行了比较。我们发现，与 25 μg rVP1 疫苗相比，仅含有 2 μg VP1 蛋白的 Exo-VP1 疫苗可诱导更强的 CVB3 特异性 T 细胞增殖和 CTL 反应（分别增加超过 70% 和 40%），并引发更多的脾 Th1/CTL 相关细胞因子（IFN-γ、TNF-α 和 IL-12）。此外，Exo-VP1 组中还证明了 IgG 水平较高，中和滴度和亲和力增加。一致的是，Exo-VP1组比rVP1疫苗表现出对病毒性心肌炎更强的抵抗力，反映在心脏病毒载量降低、心肌炎症改善和存活率提高。总的来说，我们报告 Exo-VP1 可能是比 rVP1 疫苗更有效的 CVB3 候选疫苗。
Coxsackievirus B3 (CVB3) is an important cause of viral myocarditis with no vaccine available in clinic. Herein we constructed an exosome-based anti-CVB3 vaccine (Exo-VP1), and compared its immunogenicity and immunoprotection with our previously reported recombinant VP1 protein (rVP1) vaccine. We found that compared with the 25 μg rVP1 vaccine, Exo-VP1 vaccine containing only 2 μg VP1 protein induced much stronger CVB3-specific T cell proliferation and CTL responses (with an increase of more than 70% and 40% respectively), and elicited greater splenic Th1/CTL associated cytokines (IFN-γ, TNF-α and IL-12). Furthermore, higher IgG levels with increased neutralizing titers and avidity were also evidenced in Exo-VP1 group. Consistently, Exo-VP1 group exhibited enhanced resistance to viral myocarditis than rVP1 vaccine, reflected by reduced cardiac viral loads, improved myocardial inflammation and an increased survival rate. Collectively, we reported that Exo-VP1 might present a more potent CVB3 vaccine candidate than rVP1 vaccine.