近日，国际学术刊物PLoS ONE在线发表了中科院上海巴斯德研究所黄忠课题组和中科院过程工程研究所苏志国课题组关于肠道病毒71型基因工程疫苗的合作研究成果。
手足口病是5岁以下儿童中发生的常见传染病，潜伏期为2至7天，患者的典型症状表现为发热及手、足、口腔等部位的疱疹，部分患者可引起脑干脑炎、肺水肿、心肌炎、无菌性脑膜脑炎等并发症并造成死亡。2012年，我国内地共有2，198，442个报告病例，造成569例死亡。然而，目前还没有预防手足口病的有效疫苗。
肠道病毒71型（EV71）是引起手足口病的主要病原体，包含11种亚型，其中C4亚型在中国大陆流行。因此，尽快开发出针对EV71，尤其是针对C4亚型的疫苗，对于有效预防和控制我国儿童中发生的手足口病，具有重要的意义。
上海巴斯德所疫苗学与抗病毒策略研究组博士研究生库志强等在黄忠研究员和苏志国研究员的指导下，利用基因工程手段制备了EV71病毒C4亚型的病毒样颗粒疫苗，这种病毒样颗粒保持了病毒外部形态和所有结构蛋白，但没有感染性的病毒核酸。用病毒样颗粒疫苗免疫小鼠所获得的抗血清在体外实验中可以有效保护细胞免受病毒感染，表明抗血清中存在高效价的中和抗体。
进一步研究显示抗血清中的中和抗体主要结合病毒外壳表面突起的一个保守位点。更为重要的是发现中和抗体不仅可以早期封闭病毒与细胞的结合，并且在病毒与细胞表面结合后还可以阻止病毒进入细胞，从而在抗病毒感染的过程中发挥两重抑制作用。
该项研究初步揭示了EV71病毒样颗粒疫苗的抗病毒保护机制，为开发基于病毒样颗粒的EV71基因工程疫苗奠定了基础。研究工作得到中国科学院“百人计划”和生化工程国家重点实验室开放基金的经费支持。（生物谷Bioon.com）
doi:10.1371/journal.pone.0057601
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PMID:
Neutralizing Antibodies Induced by Recombinant Virus-Like Particles of Enterovirus 71 Genotype C4 Inhibit Infection at Pre- and Post-attachment Steps
Zhiqiang Ku, Xiaohua Ye, Xulin Huang, Yicun Cai, Qingwei Liu, Yan Li, Zhiguo Su, Zhong Huang
Background Enterovirus 71 (EV71) is a major causative agent of hand, foot and mouth disease, which has been prevalent in Asia–Pacific regions, causing significant morbidity and mortality in young children. Antibodies elicited by experimental EV71 vaccines could neutralize infection in vitro and passively protect animal models from lethal challenge, indicating that neutralizing antibodies play an essential role in protection. However, how neutralizing antibodies inhibit infection in vitro remains unclear. Methods/Findings In the present study, we explored the mechanisms of neutralization by antibodies against EV71 virus-like particles (VLPs). Recombinant VLPs of EV71 genotype C4 were produced in insect cells using baculovirus vectors. Immunization with the VLPs elicited a high-titer, EV71-specific antibody response in mice. Anti-VLP mouse sera potently neutralized EV71 infection in vitro. The neutralizing antibodies in the anti-VLP mouse sera were found to target mainly an extremely conserved epitope (FGEHKQEKDLEYGAC) located at the GH loop of the VP1 protein. The neutralizing anti-VLP antisera were able to inhibit virus binding to target cells efficiently. In addition, post-attachment treatment of virus-bound cells with the anti-VLP antisera also neutralized virus infection, although the antibody concentration required was higher than that of the pre-attachment treatment. Conclusions Collectively, our findings represent a valuable addition to the understanding of mechanisms of EV71 neutralization and have strong implications for EV71 vaccine development.
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