Zhang Ming, Xu Danhan, Liu Yuhan, Wang Xiaohui, Xu Lilan, Gao Na, Feng Changzeng, Guo Wei, Ma Shaohui
Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, Kunming, China.
Yunnan Key Laboratory of Vaccine Research Development on Severe Infectious Disease, Kunming, China.
Front Microbiol. 2023 Jul 12;14:1172349. doi: 10.3389/fmicb.2023.1172349. eCollection 2023.
Coxsackievirus B1 (CVB1) is one of the significant pathogens causing viral myocarditis, hand, foot, and mouth disease (HFMD), and aseptic meningitis, and it has been associated with type 1 diabetes (T1DM). No effective antiviral drugs against CVB1 infection or preventive vaccines are available. Due to the success of two inactivated vaccines against enterovirus 71 and poliovirus, an inactivated Vero cell-based CVB1 vaccine could be developed. In this study, we isolated a high-growth CVB1 virus strain KM7 in Vero cells and developed a Vero-adapted vaccine candidate strain KM7-X29 via three rounds of plaque purification and serial passages. The KM7-X29 strain was grouped into the GII sub-genotype, which belonged to the Chinese epidemic strain and grew to a titer of more than 10 CCID50/ml in Vero cells. The inactivated CVB1 vaccine produced by the KM7-X29 strain induced an effective neutralizing antibody response in BALB/c mice, and maternal antibodies were able to provide a 100% protective effect against lethal challenges with a CVB1 strain in suckling BALB/c mice. Thus, the KM7-X29 strain might be used as a new candidate coxsackievirus B1 vaccine strain. The neonatal murine model of CVB1 infection will contribute to the development of the CVB1 vaccine.
柯萨奇病毒B1(CVB1)是引起病毒性心肌炎、手足口病(HFMD)和无菌性脑膜炎的重要病原体之一,并且与1型糖尿病(T1DM)有关。目前尚无针对CVB1感染的有效抗病毒药物或预防性疫苗。鉴于两种针对肠道病毒71型和脊髓灰质炎病毒的灭活疫苗取得了成功,一种基于Vero细胞的CVB1灭活疫苗有望研发出来。在本研究中,我们在Vero细胞中分离出一种高生长性的CVB1病毒株KM7,并通过三轮蚀斑纯化和连续传代培养出一种适应Vero细胞的候选疫苗株KM7-X29。KM7-X29株被归类为GII亚基因型,属于中国流行株,在Vero细胞中生长至滴度超过10 CCID50/ml。由KM7-X29株生产的CVB1灭活疫苗在BALB/c小鼠中诱导了有效的中和抗体反应,并且母源抗体能够为哺乳的BALB/c小鼠提供100%的保护作用,使其免受CVB1毒株的致死性攻击。因此,KM7-X29株可能用作柯萨奇病毒B1新的候选疫苗株。CVB1感染的新生鼠模型将有助于CVB1疫苗的研发。