Immunogenicity and protective efficacy of a novel foot-and-mouth disease virus empty-capsid-like particle with improved acid stability
Immunogenicity and protective efficacy of a novel foot-and-mouth disease virus empty-capsid-like particle with improved acid stability
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一种具有改善酸稳定性的新型口蹄疫病毒空衣壳样颗粒的免疫原性和保护功效
DOI：
10.1016/j.vaccine.2019.02.032
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发表时间：
2019-03-28
期刊：
影响因子：
5.5
通讯作者：
Li, Zhiyong
中科院分区：
文献类型：
--
作者：
Xie, Yinli;Li, Haitao;Li, Zhiyong
口蹄疫病毒（Foot-and-mouth disease virus，FMDV）是一种危害偶蹄类动物的高度传染性疾病。FMDV衣壳是高度酸不稳定的，并且病毒颗粒在弱酸性pH下分解时失去其免疫原性。O型口蹄疫病毒的病毒衣壳比其他血清型的病毒衣壳更敏感，这使得在酸性昆虫细胞环境中获得足够的空衣壳样颗粒用于研究更加困难。本研究利用BHK-21细胞在低pH条件下培养，分离出了新的抗酸性增强的口蹄疫病毒突变株。在所有六个突变体中检测到VP 1衣壳蛋白中的氨基酸取代Q25 R、K41 E和N85 A以及VP 3衣壳蛋白中的氨基酸取代K154 Q。基于这些氨基酸替换，在昆虫细胞中产生了O型FMDV空衣壳样颗粒，其对酸诱导的衣壳解离成五聚体亚基具有抗性。我们的特点是这些耐酸空衣壳颗粒诱导的保护性免疫。用耐酸空衣壳颗粒免疫小鼠后，引起了显着的体液和细胞免疫应答。耐酸的空capsules样颗粒也能诱导豚鼠产生较强的中和抗体，对FMDV攻击具有保护作用。我们的研究结果表明，这些耐酸空衣壳样颗粒具有潜在的效用，作为疫苗对血清O型口蹄疫病毒感染。(C)2019爱思唯尔有限公司版权所有。
Foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects cloven-hoofed animal species. The FMDV capsid is highly acid labile and viral particles lose their immunogenicity when they disassemble at mildly acidic pHs. The viral capsid of FMDV serotype O is more sensitive than those of other serotypes, making it more difficult to acquire enough emptycapsid-like particles in the acidic insect cell environment for research. In this study, novel FMDV mutants with increased acid resistance were isolated using BHK-21 cell cultured under low-pH conditions. Amino acid substitutions Q25R, K41E, and N85A in the VP1 capsid protein and K154Q in the VP3 capsid protein were detected in all six mutants. Based on these amino acid replacements, empty-capsid-like particles of FMDV serotype O, which were resistant to the acid-induced dissociation of the capsid into pentameric subunits, were produced in insect cells. We characterized the protective immunity induced by these acid-resistant empty capsid particles. Significant humoral and cellular immune responses were elicited in mice after immunization with the acid-resistant empty capsid particles. The acid-resistant emptycapsid-like particles also induced strong neutralizing antibodies in guinea pigs and protected all the guinea pigs from FMDV challenge. Our results suggest that these acid-resistant empty-capsid-like particles have potential utility as a vaccine against serotype O FMDV infection. (C) 2019 Elsevier Ltd. All rights reserved.