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

开发合理减毒活疫苗以有效控制传染性支气管炎

• 批准号: BB/H01425X/1
• 负责人: Paul Britton
• 金额: $ 103.27万
• 依托单位: The Pirbright Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH01425X%2F1
• 关键词: Development; rationally; attenuated; live; vaccines

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.

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卵内应用的免疫原性。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群中普遍存在。 IBV 是传染性支气管炎 (IB) 的病原体，并继续造成鸡的经济损失、福利问题以及粮食安全的潜在风险。 IBV 优先引起呼吸道疾病，但也可能感染其他器官，例如肾脏（导致肾脏疾病）或生殖道（导致产蛋量和/或卵子质量下降）。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多。尽管减毒活疫苗和灭活疫苗普遍用于控制 IBV，但由于疫苗失效或引入与所用疫苗无关的新 IBV 血清型，通过疫苗接种获得的保护可能会丧失，从而导致给家禽业带来风险。开发新的、更安全的疫苗来控制 IBV 非常重要。该提案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，可以对其进行修改以进行减毒。该项目分为四个主要目标：- 1) 生产基于 IBV 致病性 M41 菌株的 IBV 反向遗传学系统。 2）去除M41辅助非结构基因，鉴定其是否在致病性中发挥作用。 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) 研究卵内接种IBV的减毒效果。这个高度创新的项目将由康普顿动物健康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中测试rIBV的动物设施。该提交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 疫苗接种策略放宽或疫苗接种中断，将对英国家禽业的家禽福利和生产成本产生深远的破坏性影响，并给食品安全带来相关风险。这项工作将为新的合理改良且更安全的疫苗铺平道路，因为它们不太可能恢复。开发更安全的疫苗的另一个预期好处是减少用于对抗IB相关继发细菌感染的抗生素用量。

项目成果

Reverse Genetics of RNA Viruses - Applications and Perspectives

RNA 病毒的反向遗传学 - 应用和前景

• DOI: http://dx.10.1002/9781118405338.ch2
• 发表时间: 2012
• 作者: Armesto M

Reverse Genetics System for the Avian Coronavirus Infectious Bronchitis Virus.

禽冠状病毒传染性支气管炎病毒的反向遗传学系统。

• DOI: http://dx.10.1007/978-1-4939-6964-7_6
• 发表时间: 2017
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Bickerton E

Recombinant vaccines against infectious bronchitis

传染性支气管炎重组疫苗

• 发表时间: 2012
• 期刊: Avian Pathology Newsletter
• 作者: Britton P

Infectious Bronchitis Virus as a Vector for the Expression of Heterologous Genes.

传染性支气管炎病毒作为异源基因表达的载体。

• DOI: http://dx.10.1371/journal.pone.0067875
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Bentley K

Modification of the avian coronavirus infectious bronchitis virus for vaccine development.

用于疫苗开发的禽冠状病毒传染性支气管炎病毒的修饰。

• DOI: http://dx.10.4161/bbug.18983
• 发表时间: 2012
• 期刊: Bioengineered bugs
• 作者: Britton P