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，同时保持对鸡的疫苗接种和体内应用的免疫原性。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禽类病原体，在世界各地的所有类型的禽群中流行。IBV是传染性支气管炎(IB)的病原体，并继续对经济损失、鸡的福利问题和食品安全的潜在风险负责。IBV主要导致呼吸道疾病，但也可感染其他器官，如肾脏(导致肾脏疾病)或生殖道(导致产蛋量和/或鸡蛋质量损失)。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。虽然减毒活疫苗和灭活疫苗被普遍用于控制IBV，但由于疫苗崩溃或引入与所用疫苗无关的新的IBV血清型，通过接种疫苗获得的保护可能会丧失，对家禽养殖业构成风险。重要的是开发新的更安全的疫苗来控制IBV。这项建议旨在开发一种感染性克隆系统，用于产生合理减毒的IBV疫苗，识别基因组中两个空间上相距较远的区域，这些区域可以被修改以进行减毒。该项目分为四个主要目标：-1)建立基于IBV致病株M41株的IBV反向遗传学系统。2)去除M41辅助非结构基因，以确定它们是否在致病中起作用。3)研究M41必需(复制酶)非结构蛋白基因在致病中的作用。4)探讨IBV体内接种的减毒效果。这一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，该研究所拥有必要的IBV反向遗传学技术和在鸡身上测试rIBV的动物设施。这份意见书是对家禽研究委员会在2008年11月17日的会议上确定和同意的研究要求的直接回应。对食物链的预期好处：放松IBV疫苗接种策略或由于新的IBV毒株而导致疫苗接种中断，将在禽鸟福利和生产成本方面对英国家禽业产生深远和毁灭性的影响，并对食品安全构成相关风险。这项工作将为新的合理修改和更安全的疫苗铺平道路，因为它们将不太可能恢复。开发更安全的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的量。

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.