An Albumin-Binding Domain Peptide Confers Enhanced Immunoprotection Against Viral Myocarditis by CVB3 VP1 Vaccine.
An Albumin-Binding Domain Peptide Confers Enhanced Immunoprotection Against Viral Myocarditis by CVB3 VP1 Vaccine.
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白蛋白结合域肽通过 CVB3 VP1 疫苗增强针对病毒性心肌炎的免疫保护
DOI：
10.3389/fimmu.2021.666594
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发表时间：
2021
影响因子：
7.3
通讯作者：
Xiong S
中科院分区：
文献类型：
--
作者：
Gao Y;Yue Y;Xiong S
柯萨奇病毒B3 （CVB3）诱导的病毒性心肌炎是一种常见的临床心血管疾病，目前尚无有效的疫苗。在这项研究中，我们试图通过引入一种链球菌蛋白g源性引流淋巴结（dLNs）靶向白蛋白结合域（ABD）肽来增强先前cvb3特异性VP1蛋白疫苗的免疫保护效果。我们发现，与原VP1疫苗相比，ABD-VP1 （ABD-VP1）疫苗在体外和体内都获得了有效结合小鼠白蛋白的新能力，在免疫后血清中具有更长的血清半衰期，并且在dln中具有更高的丰度。因此，ABD-VP1免疫不仅显著促进树突状细胞（dc）的富集和成熟，在dln中诱导更高比例的IFN-γ+ CD8 +细胞，而且显著促进vp1诱导的脾脏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和脾脏中诱导了更高百分比的保护性CD44hi - cd62hi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，心功能改善，心脏组织形态学改变减轻，28天生存率提高。我们的结果表明，ABD可能是一种很有前途的疫苗设计和开发的免疫增强机制。
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 CD44hi CD62Lhi 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.
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DOI：
10.1007/978-1-0716-0771-8_12
发表时间：
2020-01-01
期刊：
GAPMERS
影响因子：
--
作者：
Cai, Yunpeng;Lou, Chenguang;Howard, Kenneth A.
通讯作者：
Howard, Kenneth A.
影响因子：
7.2
作者：
Macedo, Rodney;Rochefort, Juliette;Lemoine, Francois M.
通讯作者：
Lemoine, Francois M.
影响因子：
32.4
作者：
Baptista, Antonio P.;Gola, Anita;Germain, Ronald N.
通讯作者：
Germain, Ronald N.
影响因子：
4.8
作者：
Johansson, MU;Frick, IM;Wikström, M
通讯作者：
Wikström, M
影响因子：
10.8
作者：
Alfonso Rojas, Luis;Condezo, Gabriela N.;Alemany, Ramon
通讯作者：
Alemany, Ramon