Development of rationally attenuated live vaccines for effective control of infectious bronchitis

该项目的总体目标是以不可逆的方式减弱家禽传染性支气管炎病毒（IBV）的致病性，同时保持鸡疫苗接种和蛋内应用的免疫原性。控制传染病和减少治疗性抗生素的使用是英国家禽业面临的两大挑战。禽冠状病毒（IBV）是一种高度传染性的家禽病原体，在全世界所有类型的家禽中普遍存在。IBV是传染性支气管炎（IB）的致病因子，并继续造成经济损失、鸡的福利问题和对粮食安全的潜在风险。IBV主要引起呼吸道疾病，但也可感染其他器官，如肾脏（导致肾脏疾病）或生殖道（导致产蛋量下降和/或鸡蛋质量下降）。据报道，IBV对英国家禽业造成的经济损失比任何其他传染病都要大。虽然在控制IBV方面普遍使用减毒活疫苗和灭活疫苗，但由于疫苗失效或引入与所用疫苗无关的新的IBV血清型，使用疫苗接种获得的保护可能会丧失，从而对家禽业构成风险。重要的是为控制IBV开发新的和更安全的疫苗。本提案旨在开发一个传染性克隆系统，用于生产合理减毒的IBV疫苗，确定两个空间上遥远的基因组区域，可以进行修饰以进行减毒。该项目分为四个主要目标：- 1)以IBV致病性M41株为基础，建立IBV反向遗传系统。2)去除M41附属非结构基因，确定其是否在致病性中起作用。3)研究M41必需（复制酶）非结构蛋白基因在致病性中的作用。4)探讨疫苗接种对IBV的抑制作用。这个高度创新的项目将由康普顿动物卫生研究所的冠状病毒研究小组进行，该小组拥有必要的IBV反向遗传技术和动物设施，可以在鸡身上测试ribv。该报告是对家禽研究委员会在2008年11月17日会议上确定并同意的研究要求的直接回应。对食物链的预期好处：由于新的IBV菌株，IBV疫苗接种策略的放松或疫苗接种的中断将对英国家禽业在鸟类福利和生产成本方面产生深远和破坏性的影响，并对粮食安全带来相关风险。这项工作将为合理修改和更安全的新疫苗铺平道路，因为它们不太可能恢复。开发更安全疫苗的另一个预期好处是减少用于对抗与IB相关的继发性细菌感染的抗生素数量。

The overall aim of this project is to attenuate the pathogenicity of infectious bronchitis virus (IBV) of poultry in a non-reversible way, whilst maintaining immunogenicity for both vaccination of chickens and for in ovo application. Control of infectious diseases and a reduction in the use of therapeutic antibiotics are two major challenges faced by the UK poultry industry. The avian coronavirus, IBV, is a highly contagious poultry pathogen prevalent in all types of poultry flocks worldwide. IBV is the causal agent of infectious bronchitis (IB) and continues to be responsible for economic loss, welfare problems in chickens and a potential risk to food security. IBV preferentially causes respiratory disease, but can also infect other organs such as the kidneys (resulting in kidney disease) or the reproductive tract (resulting in loss of egg production and/or egg quality). IBV has been reported to be responsible for more economic loss to the UK poultry industry than any other infectious disease. Although live attenuated vaccines and inactivated vaccines are universally used in the control of IBV, the protection gained by use of vaccination can be lost either due to vaccine breakdown or the introduction of a new IBV serotype that is not related to the vaccine used, posing a risk to the poultry industry. It is important that new and safer vaccines are developed for the control of IBV. This proposal seeks to develop an infectious clone system for the generation of rationally attenuated IBV vaccines, identifying two spatially distant regions of the genome that can be modified for attenuation. The project is divided into four main objectives:- 1) To produce an IBV reverse genetics system based on the pathogenic M41 strain of IBV. 2) To remove the M41 accessory non-structural genes to identify whether they play a role in pathogenicity. 3) To study the role of the M41 essential (replicase) non-structural protein genes in pathogenicity. 4) To investigate the attenuation of IBV for in ovo vaccination. This highly innovative project will be carried out by the coronavirus research group at the Institute for Animal Health, Compton which has the necessary IBV reverse genetics technology and the animal facilities to test rIBVs in chickens. The submission is in direct response to research requirements identified and agreed by the Poultry Research Committee at their meeting on the 17th November 2008. Expected benefits to the food chain: Relaxation of IBV vaccination strategies or the breakdown of vaccination, due to new IBV strains, would have a profound and devastating affect on the UK poultry industry in terms of bird welfare and production costs, with associated risks to food security. This work will pave the way for new rationally modified and safer vaccines, as they will be less likely to revert. A further expected benefit from the development of safer vaccines, is a reduction in the amount of antibiotics used to counteract secondary bacterial infections associated with IB.