Vaccine Research Center, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Vaccine Research Center, CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, 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.
Vaccine. 2018 Jan 29;36(5):653-659. doi: 10.1016/j.vaccine.2017.12.057. Epub 2017 Dec 30.
Enterovirus D68 (EV-D68) is increasingly associated with severe acute respiratory infection and acute flaccid myelitis (AFM) in children around the world. However, neither vaccines nor therapeutic drugs are available for EV-D68. Here we report the development of a virus-like particle (VLP) based experimental EV-D68 vaccine. We found that EV-D68 VLPs could be successfully generated in insect cells infected with a recombinant baculovirus co-expressing the P1 precursor and 3CD protease of EV-D68. Biochemical and electron microscopic analyses revealed that EV-D68 VLPs were composed of VP0, VP1, and VP3 capsid proteins derived from precursor P1 and were visualized as spherical particles of ∼30 nm in diameter. Immunization of mice with EV-D68 VLPs resulted in the production of serum antibodies that displayed potent serotype-specific neutralizing activities against EV-D68 virus in vitro. Passive transfer of anti-VLP sera completely protected neonatal recipient mice from lethal EV-D68 infection. Moreover, maternal immunization with these VLPs provided full protection against lethal EV-D68 challenge in suckling mice. Together, these results demonstrate that the recombinant EV-D68 VLP is a promising vaccine candidate against EV-D68 infection.
肠道病毒 D68（EV-D68）在世界范围内与儿童严重急性呼吸道感染和急性弛缓性脊髓炎（AFM）的发生密切相关，但目前既没有针对 EV-D68 的疫苗，也没有治疗药物。在此，我们报告了一种基于病毒样颗粒（VLP）的 EV-D68 实验性疫苗的开发。我们发现，在共表达 EV-D68 P1 前体和 3CD 蛋白酶的重组杆状病毒感染的昆虫细胞中，可以成功生成 EV-D68 VLP。生化和电子显微镜分析表明，EV-D68 VLP 由源自前体 P1 的 VP0、VP1 和 VP3 衣壳蛋白组成，呈现出直径约 30nm 的球形颗粒。用 EV-D68 VLP 免疫小鼠可诱导产生血清抗体，该抗体在体外对 EV-D68 病毒显示出强大的血清型特异性中和活性。抗-VLP 血清的被动转移可完全保护新生受体小鼠免受致死性 EV-D68 感染。此外，这些 VLP 的母体免疫为哺乳期小鼠提供了针对致死性 EV-D68 攻击的完全保护。总之，这些结果表明，重组 EV-D68 VLP 是预防 EV-D68 感染的有前途的候选疫苗。
