近日,，國際學(xué)術(shù)刊物PLoS ONE在線發(fā)表了中科院上海巴斯德研究所黃忠課題組和中科院過程工程研究所蘇志國課題組關(guān)于腸道病毒71型基因工程疫苗的合作研究成果。
手足口病是5歲以下兒童中發(fā)生的常見傳染病，潛伏期為2至7天,，患者的典型癥狀表現(xiàn)為發(fā)熱及手、足,、口腔等部位的皰疹,，部分患者可引起腦干腦炎,、肺水腫、心肌炎,、無菌性腦膜腦炎等并發(fā)癥并造成死亡,。2012年，我國內(nèi)地共有2,，198,，442個報告病例，造成569例死亡,。然而,，目前還沒有預(yù)防手足口病的有效疫苗。
腸道病毒71型（EV71）是引起手足口病的主要病原體,，包含11種亞型,，其中C4亞型在中國大陸流行。因此,，盡快開發(fā)出針對EV71,，尤其是針對C4亞型的疫苗，對于有效預(yù)防和控制我國兒童中發(fā)生的手足口病,，具有重要的意義,。
上海巴斯德所疫苗學(xué)與抗病毒策略研究組博士研究生庫志強(qiáng)等在黃忠研究員和蘇志國研究員的指導(dǎo)下，利用基因工程手段制備了EV71病毒C4亞型的病毒樣顆粒疫苗,，這種病毒樣顆粒保持了病毒外部形態(tài)和所有結(jié)構(gòu)蛋白,，但沒有感染性的病毒核酸。用病毒樣顆粒疫苗免疫小鼠所獲得的抗血清在體外實(shí)驗(yàn)中可以有效保護(hù)細(xì)胞免受病毒感染,，表明抗血清中存在高效價的中和抗體,。
進(jìn)一步研究顯示抗血清中的中和抗體主要結(jié)合病毒外殼表面突起的一個保守位點(diǎn)。更為重要的是發(fā)現(xiàn)中和抗體不僅可以早期封閉病毒與細(xì)胞的結(jié)合,，并且在病毒與細(xì)胞表面結(jié)合后還可以阻止病毒進(jìn)入細(xì)胞,，從而在抗病毒感染的過程中發(fā)揮兩重抑制作用。
該項研究初步揭示了EV71病毒樣顆粒疫苗的抗病毒保護(hù)機(jī)制,，為開發(fā)基于病毒樣顆粒的EV71基因工程疫苗奠定了基礎(chǔ),。研究工作得到中國科學(xué)院“百人計劃”和生化工程國家重點(diǎn)實(shí)驗(yàn)室開放基金的經(jīng)費(fèi)支持。（生物谷Bioon.com）
doi:10.1371/journal.pone.0057601
PMC:
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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