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In this study, we tried to potentiate the immunoprotection efficacy of our previous <jats:italic>CVB3<\/jats:italic>-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 <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, 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<jats:italic>-\u03b3<jats:sup>+<\/jats:sup><\/jats:italic> CD8<jats:italic><jats:sup>+<\/jats:sup><\/jats:italic> 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<jats:sup>hi<\/jats:sup> CD62L<jats:sup>hi<\/jats:sup> 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.<\/jats:p>","DOI":"10.3389\/fimmu.2021.666594","type":"journal-article","created":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T05:03:15Z","timestamp":1632286995000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["An Albumin-Binding Domain Peptide Confers Enhanced Immunoprotection Against Viral Myocarditis by CVB3 VP1 Vaccine"],"prefix":"10.3389","volume":"12","author":[{"given":"Yue","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidong","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq467","article-title":"Mesenchymal Stem Cells Improve Murine Acute Coxsackievirus B3-Induced Myocarditis","volume":"32","author":"Van Linthout","year":"2011","journal-title":"Eur Heart J"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01388","article-title":"Astragaloside IV Exerts Cardioprotection in Animal Models of Viral Myocarditis: A Preclinical Systematic Review and Meta-Analysis","volume":"10","author":"Zhuang","year":"2019","journal-title":"Front Pharmacol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"99A","DOI":"10.1016\/0735-1097(93)90470-l","article-title":"Viral Myocarditis: A Paradigm for Understanding the Pathogenesis and Treatment of Dilated Cardiomyopathy","volume":"22","author":"Sole","year":"1993","journal-title":"J Am Coll Cardiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(19)30566-3","article-title":"Enterovirus Study C. 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