Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Sci Adv. 2020 May 6;6(19):eaaz2433. doi: 10.1126/sciadv.aaz2433. eCollection 2020 May.
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.
柯萨奇病毒 B（CVB）肠道病毒是常见的人类病原体，已知可导致严重疾病，包括心肌炎、慢性扩张型心肌病和无菌性脑膜炎。CVB 也被假设是 1 型糖尿病的一个致病因素。目前尚无针对 CVB 的疫苗，在这里，我们描述了一种新型六价疫苗的生成和临床前测试，该疫苗针对六种已知的 CVB 血清型。我们表明，该疫苗在鼠模型和非人类灵长类动物中具有极好的安全性，并且无需佐剂即可在两种物种中诱导针对六种血清型的强烈中和抗体反应。我们还证明，该疫苗可提供针对小鼠急性 CVB 感染的免疫，包括已知可引起病毒诱导性心肌炎的 CVB 感染。此外，它还可阻止遗传许可的小鼠模型中由 CVB 引起的糖尿病。我们的临床前概念验证研究表明，成功生成了一种具有高免疫原性的有前途的六价 CVB 疫苗，能够预防 CVB 引起的疾病。
