A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates
A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates
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DOI：
10.1126/sciadv.aaz2433
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发表时间：
2020-05-01
期刊：
影响因子：
13.6
通讯作者：
Flodstrom-Tullberg, M.
中科院分区：
文献类型：
--
作者：
Stone, V. M.;Hankaniemi, M. M.;Flodstrom-Tullberg, M.
柯萨奇病毒B（CVB）肠道病毒是常见的人类病原体，已知可引起严重疾病，包括心肌炎、慢性扩张型心肌病和无菌性脑膜炎。CVB也被假设为1型糖尿病的致病因素。目前还没有针对CVB的疫苗，在这里，我们描述了一种针对六种已知CVB血清型的新型六价疫苗的产生和临床前试验。我们表明，该疫苗在小鼠模型和非人灵长类动物中具有良好的安全性，并且在没有佐剂的情况下，它在两个物种中诱导对六种血清型的强烈中和抗体应答。我们还证明了该疫苗对小鼠急性CVB感染提供免疫力，包括已知引起病毒诱导的心肌炎的CVB感染。此外，它在遗传允许的小鼠模型中阻断CVB诱导的糖尿病。我们的临床前概念验证研究证明了成功产生具有高免疫原性的有希望的六价CVB疫苗，其能够预防CVB诱导的疾病。
Coxsackievirus B (CVB) enteroviruses are common human pathogens known to cause severe diseases including myocarditis, chronic dilated cardiomyopathy, and aseptic meningitis. CVBs are also hypothesized to be a causal factor in type 1 diabetes. Vaccines against CVBs are not currently available, and here we describe the generation and preclinical testing of a novel hexavalent vaccine targeting the six known CVB serotypes. We show that the vaccine has an excellent safety profile in murine models and nonhuman primates and that it induces strong neutralizing antibody responses to the six serotypes in both species without an adjuvant. We also demonstrate that the vaccine provides immunity against acute CVB infections in mice, including CVB infections known to cause virus-induced myocarditis. In addition, it blocks CVB-induced diabetes in a genetically permissive mouse model. Our preclinical proof-of-concept studies demonstrate the successful generation of a promising hexavalent CVB vaccine with high immunogenicity capable of preventing CVB-induced diseases.