Towards control of Infectious bronchitis virus; understanding cross-protection and the genetic plasticity of IBV

努力控制传染性支气管炎病毒；

• 批准号: BB/M012069/1
• 负责人: Lonneke Vervelde
• 金额: $ 50.93万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM012069%2F1
• 关键词: Towards; control; Infectious; bronchitis; virus

Vaccination against numerous endemic pathogens is an essential component of the poultry industry. Without these vaccines chickens would succumb to infection at an early age, reducing the productivity of the industry well below sustainable levels. Infectious bronchitis virus (IBV) is an endemic virus that causes severe disease outbreaks in chickens worldwide; it affects the global production of meat-type birds, due to problems in weight gain and quality, and egg production through decreasing the numbers and quality of eggs produced. Effective and economically viable vaccines against IBV are available, but multiple combinations of available vaccines are needed because the level of cross-protection against different IBV strains is insufficient. Poor cross-protection is the result of variation in a major surface protein of the virus (the spike (S) protein). New variant strains of IBV with differences in the S protein appear regularly in the field and, through analysis based on the sequence of the S protein, it is impossible to predict which vaccines will induce protection against the newly emerged viruses. Only elaborate and expensive testing in chickens elucidates which vaccine combination is needed to protect against a new strain of IBV.This proposal will address the seemingly unpredictable nature of the virus. The availability of a unique reverse genetics system for IBV has the potential to lead to the development of a new generation of live vaccines. In this proposal we will generate recombinant viruses that are identical, except for the immunodominant S1 subunit, of the economically most important IBV strains (M41, 4/91 and QX). Vaccination-challenge experiments with the same and with different viruses will identify if there are different degrees of protection. The causes of insufficient and unpredictable levels of cross-protection are the main focus of this study. Ultimately we will determine the key regions or epitopes on the S1 subunit of the economically most important IBV strains that are responsible for inducing protective immune responses. We will use novel "epitope fingerprinting" technology to determine the key regions (epitopes) that are recognised by the antibodies induced after vaccination. Identification of key regions following vaccination with a single IBV strain or multiple strains will allow us to determine which epitopes are needed by a vaccine to induce protection. When new virus strains emerge we will then be able to predict which vaccines will be required to induce effective protection against the new virus strain.Moreover, we will further develop our understanding of how pressure from the bird's immune responses on the virus might drive the virus to change or mutate. This will involve the passage of an IBV strain in eggs, in the same way as vaccines are produced. However, the replication of the virus will be put under immune pressure by the addition of antibodies specific for this virus. This will essentially mimic the immune pressure applied to the replicating virus, as occurs naturally after vaccination but without testing this in birds. Using contemporary deep sequencing technology we will identify the molecular changes that occur as a result of immune pressure and the process by which the virus is able to evade the applied vaccine, potentially evolving into a new variant. By understanding and manipulating the processes that govern virus adaptation after vaccination, we aim to identify ways of reducing the danger of vaccine strains changing and causing damaging disease outbreaks.Results from this proposal will provide (1) crucial information on why vaccines used to control an important avian endemic pathogen IBV fail to induce cross-protection, (2) information for the efficient use of existing vaccines and (3) the development of more efficient vaccines, thus ensuring that poultry farming remains not only a secure food source but also increases the economic competitiveness of the UK.

针对许多地方性病原体的疫苗接种是家禽业的重要组成部分。如果没有这些疫苗，鸡只会在很小的时候就死于感染，使该行业的生产力大大低于可持续水平。传染性支气管炎病毒（IBV）是一种地方性病毒，在全世界范围内引起鸡的严重疾病爆发;由于体重增加和质量问题，它影响了全球肉类禽类的生产，并通过降低所产蛋的数量和质量影响了蛋的生产。有效的和经济上可行的针对IBV的疫苗是可用的，但是需要可用疫苗的多种组合，因为针对不同IBV毒株的交叉保护水平不足。交叉保护性差是病毒主要表面蛋白（S蛋白）变异的结果。在野外经常出现具有S蛋白差异的IBV新变异株，并且通过基于S蛋白序列的分析，不可能预测哪种疫苗将诱导针对新出现的病毒的保护。只有在鸡身上进行复杂和昂贵的测试才能阐明需要哪种疫苗组合来预防新的IBV毒株。IBV独特的反向遗传学系统的可用性有可能导致新一代活疫苗的开发。在这个建议中，我们将产生重组病毒，是相同的，除了免疫显性S1亚基，经济上最重要的IBV株（M41，4/91和QX）。用相同和不同病毒进行的疫苗接种挑战实验将确定是否存在不同程度的保护。交叉保护水平不足和不可预测的原因是本研究的主要重点。最终，我们将确定经济上最重要的IBV毒株S1亚基上负责诱导保护性免疫应答的关键区域或表位。我们将使用新的“表位指纹”技术来确定疫苗接种后诱导的抗体识别的关键区域（表位）。在用单个IBV毒株或多个毒株接种疫苗后鉴定关键区域将使我们能够确定疫苗诱导保护所需的表位。当新的病毒株出现时，我们将能够预测需要哪种疫苗才能对新的病毒株产生有效的保护作用。此外，我们将进一步了解鸟类对病毒的免疫反应如何促使病毒发生变化或变异。这将涉及IBV毒株在鸡蛋中的传代，与生产疫苗的方式相同。然而，病毒的复制将通过添加针对该病毒的特异性抗体而受到免疫压力。这将基本上模拟应用于复制病毒的免疫压力，就像接种疫苗后自然发生的那样，但没有在鸟类中进行测试。利用当代深度测序技术，我们将确定由于免疫压力而发生的分子变化，以及病毒能够逃避所应用的疫苗的过程，可能演变成一种新的变体。通过了解和操纵疫苗接种后病毒适应的过程，我们的目标是确定减少疫苗株改变和引起破坏性疾病爆发的危险的方法。这项建议的结果将提供（1）关于为什么用于控制重要的鸟类地方病病原体IBV的疫苗不能诱导交叉保护的关键信息，（2）有效利用现有疫苗的信息和（3）开发更有效的疫苗，从而确保家禽养殖不仅是一种安全的食物来源，而且还提高了英国的经济竞争力。

项目成果

Professor Pete Kaiser 1964-2016.

皮特·凯泽教授，1964-2016。

• DOI: 10.1080/03079457.2016.1251745
• 发表时间: 2016
• 期刊: journal of the W.V.P.A
• 作者: Stevens M

Recombinant Infectious Bronchitis Viruses Expressing Chimeric Spike Glycoproteins Induce Partial Protective Immunity against Homologous Challenge despite Limited Replication In Vivo.

• DOI: 10.1128/jvi.01473-18
• 发表时间: 2018-12-01
• 期刊: Journal of virology
• 影响因子: 5.4
• 作者: Ellis S;Keep S;Britton P;de Wit S;Bickerton E;Vervelde L
• 通讯作者: Vervelde L