Soppela Saana, Plavec Zlatka, Gröhn Stina, Mustonen Iiris, Jartti Minne, Oikarinen Sami, Laajala Mira, Marjomäki Varpu, Butcher Sarah J, Hankaniemi Minna M
Virology and Vaccine Immunology, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Faculty of Biological and Environmental Sciences, Molecular and Integrative Bioscience Research Programme, & Helsinki Institute of Life Sciences-Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
Sci Rep. 2025 Mar 25;15(1):10198. doi: 10.1038/s41598-025-94656-0.
Coxsackievirus B1 (CVB1) is a common cause of acute and chronic myocarditis, cardiomyopathy, and meningitis. CVBs replicate in mucosal membranes. Therefore, vaccines inducing robust mucosal immune responses are needed. We investigated the immunogenicity of virus-like particles (VLP) and inactivated virus vaccines for CVB1, administered to mice either subcutaneously or intranasally, formulated with and without commercial and an experimental adjuvant. In this study, epigallocatechin-3-gallate (EGCG) was used both as a potential adjuvant and as an inactivating agent. EGCG adjuvanted CVB1-VLP enhanced immunogenicity via the parenteral route, but not intranasally. EGCG-adjuvanted and non-adjuvanted CVB1-VLPs triggered an immune response after intranasal administration, although the response remained weak. Intranasal administration of formalin-inactivated virus elicited robust CVB1-specific humoral, cellular, and mucosal immune responses, but after EGCG-inactivation, the mucosal antibody response was lower than after formalin-inactivation. To identify the link between structure and mucosal immunogenicity, we solved the structures of CVB1-VLP and formalin-inactivated CVB1 virus at resolutions ranging from 2.15 to 4.1 Å. The structural difference between VLP and formalin-inactivated CVB1 was the presence of the genome and cross-linked amino acid residues in the formalin-inactivated virus. Formalin-inactivated CVB1 vaccine shows promise for mucosal immunizations and the structural data supports the development of next-generation VLP-vaccines in the future.
柯萨奇病毒B1（CVB1）是急性和慢性心肌炎、心肌病及脑膜炎的常见病因。CVB在黏膜中复制。因此，需要能诱导强大黏膜免疫反应的疫苗。我们研究了CVB1病毒样颗粒（VLP）疫苗和灭活病毒疫苗的免疫原性，将其皮下或鼻内接种给小鼠，并分别添加或不添加商业佐剂及一种实验性佐剂。在本研究中，表没食子儿茶素-3-没食子酸酯（EGCG）既用作潜在佐剂，又用作灭活剂。EGCG佐剂的CVB1-VLP经胃肠外途径增强了免疫原性，但经鼻内途径则未增强。EGCG佐剂和非佐剂的CVB1-VLP经鼻内接种后引发了免疫反应，尽管反应仍然较弱。鼻内接种福尔马林灭活病毒可引发强大的CVB1特异性体液、细胞和黏膜免疫反应，但经EGCG灭活后，黏膜抗体反应低于福尔马林灭活后。为确定结构与黏膜免疫原性之间的联系，我们解析了CVB1-VLP和福尔马林灭活的CVB1病毒的结构，分辨率在2.15至4.1 Å之间。VLP与福尔马林灭活的CVB1之间的结构差异在于福尔马林灭活病毒中存在基因组和交联的氨基酸残基。福尔马林灭活的CVB1疫苗在黏膜免疫方面显示出前景，且结构数据支持未来开发下一代VLP疫苗。
