Combating avian influenza through systematic analysis of antigenic drift, genetic variation, and development of novel diagnostic tools and vaccines

通过系统分析抗原漂移、遗传变异以及开发新型诊断工具和疫苗来对抗禽流感

基本信息

批准号：
BB/L018853/1
负责人：
Munir Iqbal
金额：
$ 202.32万
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：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FL018853%2F1
关键词：
Combating avian influenza through systematic

项目摘要

The global poultry industry has shown great promise for increased, cost-effective production of animal protein to meet food security challenges. Poultry production has contributed significantly to economic growth in transitioning the economies of developing nations; it has helped meet goals in poverty alleviation and reduction in rural unemployment, particularly amongst women. However, the emergence and spread of the highly pathogenic avian influenza (HPAI) H5N1, and the widespread endemic presence of low pathogenicity avian influenza (LPAI) subtypes in many countries has threatened the sustainability of the sector through incurring heavy losses in both commercial and backyard poultry production. The rapid genetic evolution and potential reassortment of HPAI and LPAI subtypes in birds remains a credible threat for pandemic emergence. Control of these viruses presents formidable challenges to public health and veterinary infrastructures. Intervention programs require accurate and timely detection of virus subtypes, and typically involve ring culling of at-risk flocks, movement and trade restrictions, and vaccination campaigns. In poor countries, large scale culling has become impractical for economic, ecological and ethical reasons, since the viruses are endemic over wide regions and in multiple diverse avian species. The effectiveness and suitability of currently available diagnostic tools and vaccines is limited by insufficient laboratory capacity, the inherent diversity of wild type circulating viruses, and inadequate vaccine delivery mechanisms. The proposed research will exploit next generation biotechnological approaches to gain new knowledge and improve control strategies to minimize economic losses due to influenza within the poultry sector, and to mitigate the risk of pandemic emergence. We will examine the different epidemiology and ecology of influenza in Vietnam and Pakistan, in relationship to differing levels of industrialization of their poultry sectors, and to provide insight into the different pathways that impact on sustainable control of AIV. These studies will advance our understanding of how genetic and antigenic diversity influences the protective efficacy of vaccines and the sensitivity/specificity of diagnostic technologies. The precise determination of antigenic epitopes critical for induction of protective immunity in chickens and ducks will inform the design of more broadly effective vaccines. These broadly cross-reactive and protective AIV antigens will be integrated into proven viral vaccine vectors; we will engineer duck enteritis virus (DEV) and the herpesvirus of turkeys (HTV) to produce multivalent recombinant live vaccines capable of protecting ducks or chickens against AIV, as well as duck plague and Marek's disease, respectively. These next generation vaccines be delivered through mass vaccination strategies (in ovo) and will allow easy differentiation of infected from vaccinated birds (DIVA). We will develop novel rapid diagnostics to differentiate major AIV subtypes infecting poultry at the pen-side. These technologies have the potential to transform control strategies by empowering farmers to identify infected flocks at an early stage, and the dual protection against highly prevalent economically important diseases (duck plague and Marek's disease) will motivate uptake of the vaccine. Through our community-based study sites, we will explore farmer attitudes and perceptions regarding disease interventions, and assess the impact of novel technologies. The knowledge and improved tailored-made tools for control and management of AIV in Vietnam and Pakistan will reduce production losses and help prevent outbreaks with a high risk of zoonotic infections. In addition to direct benefits to farming communities, the improved control measures may offer substantial indirect economic, public health, environmental and social benefits to wider communities on both the national and global scale.

全球家禽业对动物蛋白的增加，具有成本效益的生产以应对粮食安全挑战表现出了巨大的希望。家禽生产在过渡发展国家经济方面为经济增长做出了重大贡献。它有助于实现缓解贫困和减少农村失业的目标，尤其是在妇女中。然而，高度致病性禽流感（HPAI）H5N1的出现和传播以及许多国家中低致病性禽流感（LPAI）亚型在许多国家中的广泛存在，威胁着该部门的可持续性，通过在商业和后院造成沉重损失，家禽生产。鸟类中HPAI和LPAI亚型的快速遗传进化和潜在的重新分类仍然是大流行出现的可信威胁。对这些病毒的控制提出了对公共卫生和兽医基础设施的巨大挑战。干预计划需要对病毒亚型进行准确，及时的检测，通常涉及危险羊群，运动和贸易限制以及疫苗接种运动的环。在贫困国家，出于经济，生态和道德原因，大规模的淘汰已变得不切实际，因为这些病毒在广泛地区和多种不同的鸟类中都是流行的。当前可用的诊断工具和疫苗的有效性和适用性受到实验室能力不足，野生型循环病毒的固有多样性以及疫苗输送机制不足的限制。拟议的研究将利用下一代生物技术方法来获得新知识并改善控制策略，以最大程度地减少家禽领域中流感的经济损失，并减轻大流行出现的风险。我们将研究越南和巴基斯坦流感的不同流行病学和生态学，与其家禽部门的工业化水平不同，并洞悉影响AIV可持续控制的不同途径。这些研究将促进我们对遗传和抗原多样性如何影响疫苗保护性和诊断技术的灵敏度/特异性的理解。抗原表位的精确确定对于诱导鸡和鸭子的保护性免疫至关重要的确切确定将为设计更广泛的疫苗的设计提供信息。这些广泛的交叉反应和保护性AIV抗原将整合到经过验证的病毒疫苗载体中。我们将设计鸭肠炎病毒（DEV）和土耳其疱疹病毒（HTV），以分别生产能够保护鸭子或鸡肉免受AIV以及鸭子瘟疫和Marek病的多价重组活疫苗。这些下一代疫苗是通过大规模疫苗接种策略（OVO）传递的，并可以轻松地从接种疫苗的鸟类（Diva）中分化。我们将开发新型的快速诊断，以区分笔侧的主要AIV亚型感染家禽。这些技术有可能通过赋予农民在早期识别感染羊群的能力来改变控制策略，并且对高度普遍的经济上重要疾病（鸭子和马雷克氏病）的双重保护将激发疫苗的吸收。通过我们基于社区的研究地点，我们将探讨农民对疾病干预措施的态度和看法，并评估新技术的影响。知识和改进的量身定制的工具来控制和管理越南和巴基斯坦的AIV，将减少生产损失，并有助于防止爆发人畜共动性感染的高风险。除了对农业社区的直接利益外，改进的控制措施还可以为国家和全球范围内的更广泛的社区提供大量间接的经济，公共卫生，环境和社会福利。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Coinfection of Chickens with H9N2 and H7N9 Avian Influenza Viruses Leads to Emergence of Reassortant H9N9 Virus with Increased Fitness for Poultry and a Zoonotic Potential.

DOI：
10.1128/jvi.01856-21
发表时间：
2022-03-09
期刊：
Journal of virology
影响因子：
5.4
作者：
Bhat S;James J;Sadeyen JR;Mahmood S;Everest HJ;Chang P;Walsh SK;Byrne AMP;Mollett B;Lean F;Sealy JE;Shelton H;Slomka MJ;Brookes SM;Iqbal M
通讯作者：
Iqbal M

First molecular characterisation of avian metapneumovirus (aMPV) in Turkish broiler flocks

土耳其肉鸡群中禽间质肺病毒 (aMPV) 的首次分子表征