Successful immunization against a parasitic nematode by vaccination with recombinant proteins
Successful immunization against a parasitic nematode by vaccination with recombinant proteins
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DOI：
10.1016/j.vaccine.2013.05.026
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发表时间：
2013-08-20
期刊：
影响因子：
5.5
通讯作者：
Matthews, Jacqueline B.
中科院分区：
文献类型：
--
作者：
Nisbet, Alasdair J.;McNeilly, Tom N.;Matthews, Jacqueline B.
人和牲畜感染寄生线虫可对健康和生产产生破坏性影响，影响发达地区和发展中地区的粮食安全。尽管进行了几十年的研究，但针对这些病原体的重组亚单位疫苗的开发在很大程度上并不成功。我们开发了一种策略，通过研究针对感染后幼虫的特异性蛋白的IgA反应，识别温带地区小型反刍动物寄生性胃肠炎的主要病原体--圆环端毛虫的保护性抗原。抗原的选择也是基于它们在宿主/寄生虫界面上的潜在免疫调节作用。因此，通过免疫蛋白质组学鉴定的8个分子的重组版本，与其他线虫候选疫苗同源性和/或具有潜在的免疫调节活性，在单一疫苗配方中接种给绵羊。疫苗被注射了三次Quil A佐剂，随后这些动物受到了模拟野外条件的反复挑战感染。将接种疫苗的保护水平与单独接种Quil A的绵羊的保护水平进行了比较。试验进行了两次。在这两个试验中，疫苗接种者在抽样期内的平均粪便蠕虫卵计数(FWECs)显著降低，产蛋量平均减少70%(试验1)和58%(试验2)。在虫卵脱落高峰期，在试验1和试验2中，疫苗组分别比对照组少掉92%和73%的虫卵。在死后，接种疫苗的成虫负担分别比对照低75%(试验1)和56%(试验2)。这些保护水平是在最终反刍动物宿主中使用线虫重组亚单位疫苗的任何系统中观察到的最高水平，表明通过接种重组亚单位疫苗鸡尾酒来控制寄生蠕虫确实是面对多重耐药的另一种选择。(C)2013年提交人。爱思唯尔有限公司出版。保留所有权利。
Infection of humans and livestock with parasitic nematodes can have devastating effects on health and production, affecting food security in both developed and developing regions. Despite decades of research, the development of recombinant sub-unit vaccines against these pathogens has been largely unsuccessful. We have developed a strategy to identify protective antigens from Teladorsagia circumcincta, the major pathogen causing parasitic gastroenteritis in small ruminants in temperate regions, by studying IgA responses directed at proteins specific to post-infective larvae. Antigens were also selected on the basis of their potential immunomodulatory role at the host/parasite interface. Recombinant versions of eight molecules identified by immunoproteomics, homology with vaccine candidates in other nematodes and/or with potential immunoregulatory activities, were therefore administered to sheep in a single vaccine formulation. The vaccine was administered three times with Quil A adjuvant and the animals subsequently subjected to a repeated challenge infection designed to mimic field conditions. Levels of protection in the vaccinates were compared to those obtained in sheep administered with Quil A alone. The trial was performed on two occasions. In both trials, vaccinates had significantly lower mean fecal worm egg counts (FWECs) over the sampling period, with a mean reduction in egg output of 70% (Trial 1) and 58% (Trial 2). During the period of peak worm egg shedding, vaccinates shed 92% and 73% fewer eggs than did controls in Trials 1 and 2, respectively. At post mortem, vaccinates had 75% (Trial 1) and 56% (Trial 2) lower adult nematode burdens than the controls. These levels of protection are the highest observed in any system using a nematode recombinant sub-unit vaccine in the definitive ruminant host and indicate that control of parasitic helminths via vaccination with recombinant subunit vaccine cocktails is indeed an alternative option in the face of multi-drug resistance. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.