Toward improved vaccines for control of avian pathogenic Escherichia coli in poultry

禽致病性大肠杆菌（APEC）由引起大肠杆菌病的多种肠道细菌组成，大肠杆菌病是一种严重的家禽顽固性疾病，给全世界的生产者带来了巨大的经济和福利成本。损失是通过死亡率增加、加工时对胴体进行谴责、饲料转换效率降低以及与预防和治疗相关的成本来实现的。家禽健康被认为对快速增长和日益富裕的全球人口的食品供应和安全至关重要，而亚太经合组织是生产力的持久障碍。大肠杆菌病常见于因饲养不良、社会等级形成、并发感染或产蛋初期受到压力的禽类。现场数据表明，在散养系统下饲养的家禽中，大肠杆菌病的发病率较高，消费者对这类产品的需求也较高，再加上到2012年取消传统的笼蛋生产（欧盟指令1999/74/EC1），预计将增加该病的发病率。病原菌间多重耐药特性的存在和转移阻碍了抗生素对大肠杆菌病的控制。此外，禁止在接近屠宰的蛋鸡和肉鸡中使用抗生素，以防止残留物进入人类食物链。在其他可用的控制办法中，疫苗接种被认为是最可行的。在大多数国家，使用含有经福尔马林灭活的暴发菌株的全细胞的疫苗来控制禽大肠杆菌病的暴发，但是免疫是短暂的并且是菌株特异性的。一种减毒活疫苗最近在美国获准用于家禽，但缺乏广泛的现场效力数据。目前尚不清楚这些疫苗是如何起作用的，也不清楚为什么长期的交叉保护反应仍然难以捉摸。为了改进现有疫苗，我们首先需要剖析它们赋予目标食物生产宿主免疫的机制。因此，在家禽业的现金和实物捐助下，我们建议用现有的灭活疫苗和活疫苗为火鸡接种疫苗，并描述；1)免疫应答与疫苗接种诱导的保护相关；Ii)先前感染是否可以防止再次感染，如果可以，通过什么机制；Iii)抗体和产生抗体的细胞在保护中的作用；Iv)是否可以使用增强特异性免疫反应的制剂（佐剂）来改善保护性免疫反应。总的来说，这些信息将为合理设计改进的疫苗奠定基础，从而引起适当性质、地点和持续时间的反应。

Avian pathogenic Escherichia coli (APEC) comprise a diverse group of enteric bacteria that cause colibacillosis, a severe and recalcitrant disease of poultry that exerts substantial economic and welfare costs upon producers worldwide. Losses are realised through increased mortality, condemnation of carcasses at processing, reduced feed conversion efficiency and costs associated with prophylaxis and treatment. Poultry health is considered vital to the supply and safety of food to a fast growing and increasingly affluent global population and APEC are a persistent impediment to productivity. Colibacillosis is common in birds subject to stress associated with poor husbandry, formation of a social hierarchy, concurrent infections or at the onset of laying. Field data indicate a higher incidence of colibacillosis in poultry reared under free-range systems and consumer demand for such produce, coupled with the abolition of traditional cages in egg production by 2012 (EU Directive 1999/74/EC1) is expected to increase the incidence of disease. Control of colibacillosis with antibiotics is hampered by the existence and transfer of multiple drug resistance traits among pathogenic strains. Additionally, antibiotic use is prohibited in layers and broilers close to slaughter to prevent residues entering the human food chain. Of the other available options for control, vaccination is considered to be the most viable. In most countries, outbreaks of avian colibacillosis are controlled using vaccines comprising whole cells of the outbreak strain inactivated with formalin, however immunity is short-lived and strain-specific. A live-attenuated vaccine has recently been licensed in the USA for use in poultry, but extensive field efficacy data are lacking. It is not understood how these vaccines work or why long-lasting cross-protective responses remain elusive. In order to improve existing vaccines, we first need to dissect the mechanisms involved in the immunity they confer in target food-producing hosts. With cash and in-kind contributions from the poultry sector, we therefore propose to vaccinate turkeys with existing killed and live vaccines and describe; i) immune responses correlated with protection induced by vaccination; ii) whether prior infection can protect against re-infection and if so, by what mechanisms; iii) the role of antibody and antibody-producing cells in protection; iv) whether protective immune responses can be improved using preparations (adjuvants) that potentiate specific immune responses. Collectively, such information will lay the foundations for rational design of improved vaccines that elicit responses of an appropriate nature, location and duration.