Unit of Vaccinology & Antiviral Strategies, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China.
Unit of Vaccinology & Antiviral Strategies, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; Joint Center for Infection and Immunity, Guangzhou Institute of Pediatrics, Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, China.
Antiviral Res. 2018 Apr;152:124-130. doi: 10.1016/j.antiviral.2018.02.016. Epub 2018 Feb 20.
Coxsackievirus A10 (CVA10) has emerged worldwide as one of the main pathogens of hand, foot, and mouth disease (HFMD) in recent years. However, there is currently no commercial vaccine available to prevent CVA10 infection. Here we report the development of a recombinant virus-like particle (VLP) based candidate vaccine for CVA10. Co-expression of the capsid protein precursor P1 and the protease 3CD of CVA10 in Pichia pastoris resulted in cleavage of P1 into three capsid subunit proteins VP0, VP1, and VP3. These three subunit proteins co-assembled into CVA10 VLPs, which were visualized as spherical particles with a diameter of ∼30 nm under electron microscope. Immunization studies showed that CVA10 VLP could efficiently induce antigen-specific serum antibodies in mice. The anti-VLP sera were able to potently neutralize homologous and heterologous CVA10 strains. Importantly, passively transferred anti-VLP sera fully protected recipient neonatal mice from lethal CVA10 infection. In addition, neonatal mice born to the VLP-immunized dams were also completely protected from CVA10 lethal challenge. Collectively, these data show that CVA10 VLP represents a promising CVA10 vaccine candidate.
近年来，柯萨奇病毒 A10（CVA10）已在全球范围内成为手足口病（HFMD）的主要病原体之一。然而，目前尚无预防 CVA10 感染的商业疫苗。在这里，我们报告了一种基于重组病毒样颗粒（VLP）的 CVA10 候选疫苗的开发。在毕赤酵母中共同表达 CVA10 的衣壳蛋白前体 P1 和蛋白酶 3CD 导致 P1 切割成三个衣壳亚单位蛋白 VP0、VP1 和 VP3。这三种亚单位蛋白共同组装成 CVA10 VLP，在电子显微镜下观察到直径约为 30nm 的球形颗粒。免疫研究表明，CVA10 VLP 可在小鼠中有效诱导抗原特异性血清抗体。抗-VLP 血清能够强烈中和同源和异源 CVA10 株。重要的是，被动转移的抗-VLP 血清可完全保护受体新生小鼠免受致死性 CVA10 感染。此外，来自 VLP 免疫母鼠的新生小鼠也完全免受 CVA10 致死性攻击的保护。总之，这些数据表明 CVA10 VLP 代表了一种有前途的 CVA10 疫苗候选物。
