Poh Chit Laa, Kirk Katherine, Chua Hui Na, Grollo Lara
Sunway University, No. 5, Jalan Universiti, Bandar Sunway, Kuala Lumpur, Selangor Darul Ehsan, 47500, Malaysia.
Swinburne University, Melbourne, Australia.
Methods Mol Biol. 2015;1348:341-50. doi: 10.1007/978-1-4939-2999-3_29.
Enterovirus 71 (EV-71) is the main causative agent of hand, foot, and mouth disease (HFMD) which is generally regarded as a mild childhood disease. In recent years, EV71 has emerged as a significant pathogen capable of causing high mortalities and severe neurological complications in large outbreaks in Asia. A formalin-inactivated EV71 whole virus vaccine has completed phase III trial in China but is currently unavailable clinically. The high cost of manufacturing and supply problems may limit practical implementations in developing countries. Synthetic peptides representing the native primary structure of the viral immunogen which is able to elicit neutralizing antibodies can be made readily and is cost effective. However, it is necessary to conjugate short synthetic peptides to carrier proteins to enhance their immunogenicity. This review describes the production of cross-neutralizing anti-peptide antibodies in response to immunization with synthetic peptides selected from in silico analysis, generation of B-cell epitopes of EV71 conjugated to a promiscuous T-cell epitope from Poliovirus, and evaluation of the neutralizing activities of the anti-peptide antibodies. Besides neutralizing EV71 in vitro, the neutralizing antibodies were cross-reactive against several Enteroviruses including CVA16, CVB4, CVB6, and ECHO13.
肠道病毒71型(EV - 71)是手足口病(HFMD)的主要病原体,手足口病通常被认为是一种儿童期轻症疾病。近年来,EV71已成为一种重要病原体,在亚洲的大规模疫情中可导致高死亡率和严重的神经并发症。一种福尔马林灭活的EV71全病毒疫苗已在中国完成III期试验,但目前临床上尚未可用。高昂的生产成本和供应问题可能会限制其在发展中国家的实际应用。能够引发中和抗体的、代表病毒免疫原天然一级结构的合成肽易于制备且具有成本效益。然而,有必要将短合成肽与载体蛋白偶联以增强其免疫原性。本综述描述了针对通过计算机分析选择的合成肽免疫产生的交叉中和抗肽抗体的制备、将EV71的B细胞表位与脊髓灰质炎病毒的通用T细胞表位偶联、以及对抗肽抗体中和活性的评估。除了在体外中和EV71外,这些中和抗体对包括CVA16、CVB4、CVB6和ECHO13在内的几种肠道病毒具有交叉反应性。