Moredun Research Institute, Pentlands Science Park, Edinburgh EH26 0PZ, United Kingdom.
Vaccine. 2013 Aug 20;31(37):4017-23. doi: 10.1016/j.vaccine.2013.05.026. Epub 2013 May 22.
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.
人体和牲畜感染寄生性线虫会对健康和生产造成严重影响，影响发达和发展中地区的粮食安全。尽管已经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仍未成功。我们通过研究针对感染后幼虫特异性蛋白的 IgA 反应，开发了一种从回旋毛线虫（Teladorsagia circumcincta）中鉴定保护性抗原的策略。回旋毛线虫是温带地区小反刍动物寄生性胃肠炎的主要病原体。我们还根据它们在宿主/寄生虫界面的潜在免疫调节作用选择了抗原。因此，通过免疫蛋白质组学鉴定的八种分子的重组版本、与其他线虫疫苗候选物的同源性以及潜在的免疫调节活性，被纳入到一个单一的疫苗配方中，用于绵羊。该疫苗使用 Quil A 佐剂进行了三次接种，然后对动物进行了重复的挑战感染，以模拟田间条件。将接种疫苗的绵羊与单独使用 Quil A 处理的绵羊的保护水平进行了比较。该试验进行了两次。在两次试验中，与单独使用 Quil A 处理的绵羊相比，接种疫苗的绵羊在整个采样期内的平均粪便虫卵计数（FEC）明显较低，卵排出量平均减少 70%（试验 1）和 58%（试验 2）。在虫卵高峰期，接种疫苗的绵羊在试验 1 和 2 中的卵排放量分别比对照组少 92%和 73%。在剖检时，接种疫苗的绵羊的成虫线虫负担比对照组低 75%（试验 1）和 56%（试验 2）。在使用确定的反刍宿主的线虫重组亚单位疫苗的任何系统中，这些保护水平是观察到的最高水平，这表明通过接种重组亚单位疫苗鸡尾酒来控制寄生性蠕虫确实是应对多药耐药性的一种替代选择。
