Development and evaluation of an inactivated coxsackievirus A16 vaccine in gerbils.

Development and evaluation of an inactivated coxsackievirus A16 vaccine in gerbils.
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Gerbils中灭活的Coxsackievivirus A16疫苗的开发和评估。

DOI:
10.1080/22221751.2022.2093132
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发表时间:
2022-12
影响因子:
13.2
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
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柯萨奇病毒A16 (CVA16)是导致人类手足口病(手足口病)的主要病原体之一,威胁着幼儿的健康,特别是在亚太国家。疫苗接种是保护儿童免受CVA16感染的有效策略。然而,目前还没有批准用于人类的CVA16疫苗。在这项研究中,我们在MRC-5细胞中分离了一株高生长的CVA16病毒株,并通过两轮空斑纯化开发了一种适应MRC-5的候选疫苗株,命名为CVA16-393。CVA16-393菌株被分为B1b亚基因型,在MRC-5细胞中培养到107 TCID50/ml以上的滴度。该菌株的VP1基因区含有主要的中和表位,在连续传代过程中表现出高度的稳定性。CVA16-393株灭活全病毒疫苗经两剂腹腔接种后,在沙鼠体内产生了有效的中和抗体反应。加强免疫1周后,中国不同地区10246、40812TXT、11203SD、TJ-224和CA16-194株的中和抗体几何平均滴度分别为137.8、97.8、113.4、64.1和122.3。25 U以上的CVA16疫苗剂量也能够在沙鼠中提供100%的交叉保护,以抵御这五种临床菌株的致命挑战。免疫间隔一周可使中和抗体滴度保持高水平至少8周。因此,由CVA16-393菌株生产的疫苗可能是有希望的。
Coxsackievirus A16 (CVA16) is one of the major pathogens responsible for human hand, foot, and mouth disease (HFMD), which has threatened the health of young children, particularly in Asia-Pacific nations. Vaccination is an effective strategy for protecting children from CVA16 infection. However, there is currently no licensed CVA16 vaccine for use in humans. In this study, we isolated a high-growth CVA16 virus strain in MRC-5 cells and developed an MRC-5-adapted vaccine candidate strain termed CVA16-393 via two rounds of plaque purification. The CVA16-393 strain was grouped into the B1b subgenotype and grew to a titre of over 107 TCID50/ml in MRC-5 cells. The VP1 gene region of this strain, which contains the major neutralizing epitopes, displayed high stability during serial passages. The inactivated whole-virus vaccine produced by the CVA16-393 strain induced an effective neutralizing antibody response in Meriones unguiculatus (gerbils) after two doses of intraperitoneal inoculation. One week after the booster immunization, the geometric mean titres of the neutralizing antibodies for the 10246, 40812TXT, 11203SD, TJ-224 and CA16-194 strains from different regions of China were 137.8, 97.8, 113.4, 64.1 and 122.3, respectively. A CVA16 vaccine dose above 25 U was also able to provide 100% cross-protection against lethal challenges with these five clinical strains in gerbils. Immunization at a one-week interval could maintain a high level of neutralizing antibody titres for at least 8 weeks. Thus, the vaccine produced by this CVA16-393 strain might be promising.
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