Coxsackievirus B3 (CVB3)-induced viral myocarditis is a common clinical cardiovascular disease without effective available vaccine. In this study, we tried to potentiate the immunoprotection efficacy of our previous CVB3-specific VP1 protein vaccine by introducing a streptococcal protein G-derived, draining lymph nodes (dLNs)-targeting albumin-binding domain (ABD) peptide. We found that compared with the original VP1 vaccine, ABD-fused VP1 (ABD-VP1) vaccine gained the new ability to efficiently bind murine albumin both in vitro and in vivo, possessed a much longer serum half-life in serum and exhibited more abundance in the dLNs after immunization. Accordingly, ABD-VP1 immunization not only significantly facilitated the enrichment and maturation of dendritic cells (DCs), induced higher percentages of IFN-γ⁺ CD8⁺ cells in the dLNs, but also robustly promoted VP1-induced T cell proliferation and cytotoxic T lymphocyte (CTL) responses in the spleens. More importantly, ABD-VP1 also elicited higher percentages of protective CD44^hi CD62L^hi memory T cells in dLNs and spleens. Consequently, obvious protective effect against viral myocarditis was conferred by ABD-VP1 vaccine compared to the VP1 vaccine, reflected by the less body weight loss, improved cardiac function, alleviated cardiac histomorphological changes and an increased 28-day survival rate. Our results indicated that the ABD might be a promising immune-enhancing regime for vaccine design and development.

柯萨奇病毒 B3 (CVB3)病毒性心肌炎是临床常见的心血管疾病，尚无有效疫苗可用。在这项研究中，我们试图增强我们之前的免疫保护功效CVB3 - 特异性 VP1 蛋白疫苗，引入链球菌蛋白 G 衍生的引流淋巴结 (dLN) 靶向白蛋白结合域 (ABD) 肽。我们发现，与原始VP1疫苗相比，ABD融合VP1（ABD-VP1）疫苗获得了有效结合鼠白蛋白的新能力体外和体内，在血清中具有更长的血清半衰期，并且在免疫后在 dLN 中表现出更多的丰度。因此，ABD-VP1免疫不仅显着促进树突状细胞（DC）的富集和成熟，诱导更高百分比的IFN -γ ⁺ CD8 ⁺ dLN 中的细胞，而且还强烈促进了 VP1 诱导的脾脏中 T 细胞增殖和细胞毒性 T 淋巴细胞 (CTL) 反应。更重要的是，ABD-VP1 还在 dLN 和脾脏中引发更高比例的保护性 CD44 ^hi CD62L ^hi记忆 T 细胞。因此，与VP1疫苗相比，ABD-VP1疫苗对病毒性心肌炎具有明显的保护作用，表现为体重减轻较少，心功能改善，心脏组织形态学变化减轻，28天存活率提高。我们的结果表明，ABD 可能是疫苗设计和开发的一种有前途的免疫增强机制。