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Vaccine:黄忠等发现柯萨奇A16型病毒的保护性抗体表位

  1. A16型病毒
  2. Vaccine
  3. 抗体表位
  4. 柯萨奇
  5. 黄忠

来源:上海巴斯德所 2013-07-30 20:34

日前,国际学术期刊《疫苗学》Vaccine在线发表了上海巴斯德所黄忠研究组题为“Identification of conserved neutralizing linear epitopes within the VP1 protein of coxsackievirus A16”的研究论文。

日前,国际学术期刊《疫苗学》Vaccine在线发表了上海巴斯德所黄忠研究组题为“Identification of conserved neutralizing linear epitopes within the VP1 protein of coxsackievirus A16”的研究论文。该论文首次报道了柯萨奇A16型病毒(CA16)的保守线性中和表位,为设计针对CA16的广谱性多肽疫苗奠定了基础。

CA16是引起手足口病的主要病原之一。该疾病是五岁以下儿童常见传染病,有可能导致严重的神经系统损伤甚至死亡。仅今年1月至2月,我国内地报告94,693个病例,其中20例死亡。然而,到目前为止,仍无有效疫苗和治疗药物。

上海巴斯德所黄忠研究组的前期工作发现,CA16灭活病毒疫苗和CA16病毒样颗粒新型疫苗均能在小鼠体内诱导产生中和性抗血清,所产生的抗血清能够有效保护CA16病毒感染的小鼠,说明中和抗体在体内可以抵抗CA16病毒感染。

基于病毒中和抗体表位的多肽疫苗是一种新型疫苗策略,由免疫原性和保护活性位点明确鉴定的多肽构成,避免了灭活全病毒疫苗中病毒核酸或其它非保护性蛋白可能引起的副作用。然而,截至目前,能够诱导中和抗体产生的CA16中和表位尚未被鉴定出来,限制了CA16多肽疫苗的研发。

上海巴斯德所博士研究生石金平等在黄忠研究员指导下,利用该课题组前期研究获得的CA16的病毒样颗粒中和性抗血清,首先评价了CA16衣壳蛋白重叠多肽与中和性抗血清的结合能力及其中和抑制作用,筛选出候选的CA16的线性中和表位肽;然后用候选多肽免疫动物并进行了抗血清中和效果评价,确定了位于VP1蛋白上的六个线性中和表位PEP32、PEP37、PEP55、PEP63、PEP71和PEP91;通过分析获得的CA16中和表位的序列保守性和空间位置,发现这六个中和表位在CA16的不同亚型中高度保守。

本研究的完成不仅加深了我们对CA16抗原结构的认识,而且为研发安全有效的CA16广谱疫苗打下基础。

该研究工作得到中国科学院“百人计划”的经费支持。(生物谷Bioon.com)

Identification of conserved neutralizing linear epitopes within the VP1 protein of coxsackievirus A16

Jinping Shi, Xulin Huang, Qingwei Liu, Zhong Huang,

Coxsackievirus A16 (CA16) is a major causative agent of hand, foot, and mouth disease. Immunization with inactivated whole-virus or recombinant virus-like particles (VLP) of CA16 elicits neutralizing antibodies that protect mice against lethal challenge. However, the epitope/s responsible for this induction has not been determined. In this investigation, we identified six neutralizing linear epitopes of CA16. A panel of 95 synthetic peptides spanning the entire VP1 protein of CA16 were screened by ELISA for reactivity with neutralizing antisera against CA16 VLPs, which were generated in a previous study (Vaccine 30:6642–6648). Fifteen high-binding peptides were selected and further examined for their inhibitory effect on neutralization by anti-VLP sera. Among them, six peptides with no overlap significantly inhibited neutralization. Mice immunized with these six peptides generated peptide-specific serum antibodies. The anti-peptide antisera positively detected CA16 via immunofluorescent staining and Western blot assays. More importantly, they neutralized both homologous and heterologous CA16 strains, indicating that these six peptides represented neutralizing epitopes. Sequence alignment also showed that these epitopes are extremely conserved among CA16 strains of different genotypes. These findings have important implications for the development of peptide-based broadly protective CA16 vaccines.

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