Qian Shaoju, Li Ruixue, Chen Guanyu, Ma Yinghua, Zhang Xuehan, Tang Zhou, Song Yihang, Xu Zhishan, Zhang Zihan, He Yeqing, Zhang Xingyi, Lu Shuao, Yang Zishan, Song Xiangfeng, Yu Wenfa, Yu Lili
School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, 453003, China.
Xinxiang Key Laboratory of Tumor Vaccine and Immunotherapy, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang,453003, China.
Virulence. 2025 Dec;16(1):2481657. doi: 10.1080/21505594.2025.2481657. Epub 2025 May 14.
Viral myocarditis (VM) is an inflammatory disease posing a serious threat to public health, with various viral pathogens contributing to its pathogenesis. Coxsackievirus B3 (CVB3) is the most frequently implicated causative agent and has been extensively studied because of its high prevalence and severity. No specific therapeutic interventions for VM exist, and vaccine development has encountered substantial challenges. Therefore, we aimed to develop a novel CVB3 mucosal vaccine as a preventive strategy against VM. Gram-positive enhancer matrice (GEM) particles serve as innovative mucosal vaccine adjuvants and antigen delivery systems that enhance antigen immunogenicity by facilitating effective mucosal immune responses. In this study, GEM particle display technology was used to develop two novel CVB3 vaccines: (1) a GEM particle-based vaccine displaying the CVB3 capsid protein VP1 via a PA anchor protein (GEM-PA-VP1), and (2) a GEM particle-based vaccine displaying VP1 via the FcSP peptide (GEM-Fc-VP1). Both GEM-PA-VP1 and GEM-Fc-VP1 vaacines significantly elevated levels of specific IgG, IgG1, IgG2a, sIgA and neutralizing antibodies in a mouse model, along with enhanced secretion of Th1- and Th2-associated cytokines, compared to controls. Notably, GEM-Fc-VP1 demonstrated superior immunogenicity compared with that of GEM-PA-VP1, evidenced by higher antibody titres and cytokine responses. In challenge protection experiments, both vaccines significantly improved survival rates, reduced myocardial enzyme levels, and decreased inflammatory cell infiltration in myocardial tissue, with GEM-Fc-VP1 exhibiting greater efficacy. These findings establish a foundation for the development of a safe and effective CVB3 candidate vaccine and provide novel insights into the potential of peptide-mediated subunit vaccine approaches.
病毒性心肌炎（VM）是一种对公众健康构成严重威胁的炎症性疾病，多种病毒病原体参与其发病机制。柯萨奇病毒B3（CVB3）是最常涉及的病原体，因其高流行率和严重性而受到广泛研究。目前尚无针对VM的特异性治疗干预措施，疫苗开发也面临重大挑战。因此，我们旨在开发一种新型CVB3黏膜疫苗作为预防VM的策略。革兰氏阳性增强基质（GEM）颗粒作为创新的黏膜疫苗佐剂和抗原递送系统，通过促进有效的黏膜免疫反应来增强抗原免疫原性。在本研究中，利用GEM颗粒展示技术开发了两种新型CVB3疫苗：（1）一种基于GEM颗粒的疫苗，通过PA锚定蛋白展示CVB3衣壳蛋白VP1（GEM-PA-VP1），以及（2）一种基于GEM颗粒的疫苗，通过FcSP肽展示VP1（GEM-Fc-VP1）。与对照组相比，GEM-PA-VP1和GEM-Fc-VP1疫苗均显著提高了小鼠模型中特异性IgG、IgG1、IgG2a、sIgA和中和抗体的水平，同时增强了Th1和Th2相关细胞因子的分泌。值得注意的是，GEM-Fc-VP1表现出比GEM-PA-VP1更强的免疫原性，抗体滴度和细胞因子反应更高证明了这一点。在攻毒保护实验中，两种疫苗均显著提高了存活率，降低了心肌酶水平，并减少了心肌组织中的炎性细胞浸润，GEM-Fc-VP1表现出更高的疗效。这些发现为开发安全有效的CVB3候选疫苗奠定了基础，并为肽介导的亚单位疫苗方法的潜力提供了新的见解。
