Protecting poultry from avian influenza, Newcastle disease, infectious bronchitis, and Gumboro disease with a single dose of a multivalent vaccine

使用单剂多价疫苗保护家禽免受禽流感、新城疫、传染性支气管炎和冈伯罗病

• 批准号: BB/W003325/1
• 负责人: Munir Iqbal
• 金额: $ 57.2万
• 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: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FW003325%2F1
• 关键词: Protecting; poultry; avian; influenza; Newcastle

Poultry is one of the fastest-growing sectors that is playing a major role in the provision of food security, economic development and poverty reduction. The demand for poultry meat and eggs has been increasing exponentially in recent years with the current annual population of poultry reaching over 50,000 million. This estimates that poultry production continues to grow by 24% in the next decade. However, the biggest threat in the sustainability of poultry production is the hyper prevalence of a multitude of infectious pathogens, such as different subtypes (H5, H7 and H9) of avian influenza viruses (AIV), Newcastle disease virus (NDV) and infectious bronchitis virus (IBV) and infectious bursal disease virus (IBDV). An estimated production loss from these pathogens account for at least 20% in many regions around the globe. Primarily, the control against these diseases is achieved through vaccination. However, the effectiveness of most of the current vaccines is suboptimal, where they may only reduce the manifestation of clinical disease and mortality, but infected animals continue to shed viruses resulting in a continual chain of infections to susceptible naïve and vaccinated animals resulting in reduced weight gain in meat birds and reduced egg production and quality in layers and breeder flocks. For example, despite the hyper deployment of multiple repeated doses of each vaccine for each target disease, the manifestation of pathogens continues in the form of endemic prevalence and farmers continue to bear debilitating losses with sometimes up to 100% flock mortality or loss of egg production and zoonotic infection threats in the case of AIV. Current vaccines carry several inherent drawbacks including (i) one vaccine per disease which require multiple vaccinations and multiple bird handling resulting in expensive vaccination programmes; (ii) vaccines are given to chickens during the first three weeks of age, during this time period, birds carry maternally derived antibodies (MDA) which interferes with the vaccine performance and the efficacy of vaccines is reduced significantly; (iii) vaccines are produced in the eggs that are not ideal and requires replacement with cell culture systems; (iv) vaccines are not compatible for easy differentiation of infected from vaccinated animals (DIVA), therefore, disease-free status cannot be reclaimed easily in endemic disease regions. Therefore, new innovative vaccines are needed that could overcome these challenges.This proposal plans to address these challenges and to develop a multivalent vaccine formulation that offers protection to chickens from up to six major pathogens (AIV-H5, AIV-H7, AIV-H9, NDV, IBV, IBDV). This project will be built on our novel Target Antigen Delivery Vaccine (TADV) platform which selectively delivers vaccine antigens to chicken immune cells and potentiate antigen-specific immune response. Our studies have provided evidence that a single dose of our TADV vaccine containing modified haemagglutinin (HA) antigen fused to the antibody that specifically binds to chicken antigen-presenting cells (APCs) induced significantly faster, higher and more durable immune response in MDA positive chickens compared to the untargeted counterpart or the conventional killed virus vaccines. Here, we will use our TADV technology and develop a multivalent TADV formulation in which a single dose will contain up to six immunogenic antigens from different viruses including (AIV-H5, AIV-H7, AIV-H9, NDV, IBV, IBDV). This multivalent vaccine can be delivered to day-old chickens at the hatchery overcoming MDA inference and inducing highly protective immunity in vaccinated birds. Availability of such novel protective and cost-effective disease control tools and strategies should minimise the impact of infectious diseases on farm animals, and offer substantial indirect economic, public health, environmental and social benefits globally.

家禽是增长最快的部门之一，在提供粮食安全、经济发展和减贫方面发挥着重要作用。近年来，对禽肉和禽蛋的需求呈指数级增长，目前每年的禽类数量超过5万只。该机构预计，未来十年家禽产量将继续增长24%。然而，家禽生产可持续发展的最大威胁是多种传染性病原体的过度流行，如不同亚型(H5、H7和H9)的禽流感病毒(AIV)、新城疫病毒(NDV)、传染性支气管炎病毒(IBV)和传染性法氏囊病病毒(IBDV)。据估计，在全球许多地区，这些病原体造成的产量损失至少占20%。对这些疾病的控制主要是通过接种疫苗实现的。然而，目前大多数疫苗的效果并不理想，它们可能只会减少临床疾病的表现和死亡率，但受感染的动物继续释放病毒，导致易感幼稚和接种疫苗的动物持续感染链，导致肉禽体重增加减少，蛋鸡和种鸡群的产蛋量和质量下降。例如，尽管为每种目标疾病大量重复接种每种疫苗，但病原体继续以地方性流行的形式表现出来，农民继续承受令人衰弱的损失，有时高达100%的禽群死亡或鸡蛋产量损失和人畜共患感染威胁。目前的疫苗有几个固有的缺点，包括(I)每种疾病一种疫苗，需要多次接种疫苗和多次处理禽类，导致接种计划昂贵；(Ii)在鸡出生后的头三个星期给鸡接种疫苗，在这段时间里，禽类携带母源抗体(MDA)，干扰疫苗的性能，疫苗的效力显著降低；(Iii)疫苗是在不理想的鸡蛋中生产的，需要更换细胞培养系统；(Iv)疫苗不兼容，难以区分受感染的动物和已接种疫苗的动物(DIVA)，因此在流行地区不容易恢复无病状态。因此，需要新的创新疫苗来克服这些挑战。本提案计划应对这些挑战，并开发一种多价疫苗配方，为鸡提供对多达六种主要病原体(AIV-H5、AIV-H7、AIV-H9、新城疫、IBV、IBDV)的保护。该项目将建立在我们的新型靶向抗原递送疫苗(TADV)平台上，该平台可以选择性地将疫苗抗原递送到鸡的免疫细胞，并增强抗原特异性免疫反应。我们的研究表明，与非靶向疫苗或传统灭活病毒疫苗相比，我们的含有修饰血凝素(HA)抗原的TADV疫苗与与鸡抗原提呈细胞(APC)特异性结合的抗体融合后，在MDA阳性鸡中诱导的免疫反应显著更快、更高和更持久。在这里，我们将使用我们的TADV技术，开发一种多价TADV配方，其中一剂将包含多达六种不同病毒的免疫原性抗原，包括(AIV-H5、AIV-H7、AIV-H9、新城疫、IBV、IBDV)。这种多价疫苗可以在孵化场接种给1日龄的雏鸡，克服丙二醛的干扰，并在接种疫苗的禽类中诱导高度保护性免疫。这种新的保护性和成本效益高的疾病控制工具和战略的可获得性应将传染病对农场动物的影响降至最低，并在全球范围内提供可观的间接经济、公共卫生、环境和社会效益。