Effects of co-infections on Marek's disease in poultry and development of novel recombinant Marek's disease virus vector vaccines

混合感染对家禽马立克氏病的影响及新型重组马立克氏病病毒载体疫苗的研制

• 批准号: BB/X017575/1
• 负责人: YONGXIU YAO
• 金额: $ 58.23万
• 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: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FX017575%2F1
• 关键词: Effects; co; infections; Marek; disease

Marek's disease (MD) causes paralysis and tumours in chickens. It is caused by serotype 1 strains of the Marek's disease virus (MDV-1) which is shed from skin of infected chickens and persists for many months in dust in contaminated poultry houses. It is highly contagious and spreads to other chickens by inhalation. MD is a major disease affecting poultry health, welfare, and productivity, with annual estimated loss to the global poultry industry of $2 billion. MD is endemic in UK poultry but is effectively controlled by live vaccine viruses, which are harmless relatives of MDV-1, and include CVI988, HVT, and MDV serotype 2 (MDV-2). MDV-2 vaccines are widely used in the Americas and Asia but not in the UK. However, by testing samples collected from poultry farms, we found MDV-2 is widespread in the UK. MDV-2 strains circulate freely and naturally at high levels and persist long-term in the flock, but little is known about them; are they derived from vaccine strains which 'escaped' from imported poultry, or are they naturally occurring strains? Chickens can be infected with any combination of MDV-1, MDV-2, and vaccine viruses at the same time (co-infection). We have found MDV-2 in healthy chicken flocks, as well as flocks that have MD. We would like to know whether co-infection with MDV-2 affects flock health and disease, and production parameters such as egg production and mortality, and whether certain MDV-2 strains could be used as effective recombinant vaccines against MD and other poultry diseases. Our objectives are to: (1) Investigate prevalence of naturally occurring MDV-2 infection in the field, and it's influence on flock productivity, immune responses and disease, (2) Characterise MDV-2 field isolates and (3) Exploit novel MDV-2 as potential viral vectors for novel recombinant vaccines.The project is a partnership with poultry industry vets. We will select two MDV-2-positive and two MDV-2-negative flocks for two bird types (broiler-breeder, layer) for regular sampling to collect blood samples from chickens and dust from the housing sheds. We will also collect data on flock health and productivity. At Pirbright, we will test the samples by 'polymerase chain reaction' to detect the genetic material of MDV-1, MDV-2 and vaccine viruses to show the kinetics of MDV-2 infection and shedding, and the frequency of co-infection with MDV-1 field strains and vaccine viruses. Using mathematical modelling, we will also investigate dynamics of transmission of MDV-2 within flocks. We will determine variability of MDV-2 strains by sequencing the virus genetic material and comparing with known MDV-2 strains. We will study the characteristics of selected MDV-2 strains by growing these viruses in cell culture then using them to infect chickens under controlled laboratory conditions to examine replication, persistence, clinical signs and transmission of MDV-2. Most MDV-2 strains have characteristics which make them suitable as vaccines against MD: they do not cause disease, they grow well in the chicken and persist for many months, and they are easily transmitted between chickens to maintain a high level of exposure of the flock to vaccine virus. Furthermore, MDV-2 can be genetically engineered to carry genes from other important poultry viral pathogens, e.g., infectious bursal disease virus (IBDV) and Newcastle disease virus (NDV); a recombinant 'vectored vaccine' like this could potentially protect chickens against IBD and ND as well as MD in a single vaccination. We will engineer an appropriate MDV-2 strain to create a 'rMDV2-IBD-ND' virus, then test its ability to protect chickens against these three diseases under controlled laboratory conditions.This study is important to understand the effect of widespread MDV-2 infection on health and productivity of commercial poultry flocks. A new recombinant MDV-2 vaccine would be a useful addition to the set of live virus vaccines used to control MD and other poultry diseases.

马立克氏病 (MD) 会导致鸡瘫痪和肿瘤。它是由马立克氏病病毒 (MDV-1) 血清型 1 株引起，该病毒从受感染鸡的皮肤上脱落，并在受污染禽舍的灰尘中持续存在数月。它具有高度传染性，通过吸入传播给其他鸡。 MD 是一种影响家禽健康、福利和生产力的主要疾病，估计每年给全球家禽业造成 20 亿美元的损失。 MD 是英国家禽的地方病，但可以通过活疫苗病毒有效控制，活疫苗病毒是 MDV-1 的无害近亲，包括 CVI988、HVT 和 MDV 血清型 2 (MDV-2)。 MDV-2 疫苗在美洲和亚洲广泛使用，但在英国尚未使用。然而，通过检测从家禽养殖场收集的样本，我们发现 MDV-2 在英国广泛传播。 MDV-2 毒株在鸡群中自由、自然地高水平传播，并在鸡群中长期存在，但人们对它们知之甚少；它们是源自从进口家禽中“逃逸”的疫苗株，还是天然存在的毒株？鸡可以同时感染 MDV-1、MDV-2 和疫苗病毒的任意组合（共同感染）。我们在健康鸡群以及患有 MD 的鸡群中发现了 MDV-2。我们想知道MDV-2的共同感染是否会影响鸡群健康和疾病，以及产蛋量和死亡率等生产参数，以及某些MDV-2毒株是否可以用作针对MD和其他家禽疾病的有效重组疫苗。我们的目标是：(1) 调查现场自然发生的 MDV-2 感染的流行情况，及其对鸡群生产力、免疫反应和疾病的影响，(2) 描述 MDV-2 现场分离株的特征，以及 (3) 利用新型 MDV- 2 作为新型重组疫苗的潜在病毒载体。该项目是与家禽业兽医的合作伙伴关系。我们将为两种禽类（肉种鸡、蛋鸡）选择两只 MDV-2 阳性鸡群和两只 MDV-2 阴性鸡群进行定期采样，收集鸡只的血液样本和鸡舍灰尘样本。我们还将收集有关鸡群健康和生产力的数据。在皮尔布赖特，我们将通过“聚合酶链式反应”对样本进行检测，检测MDV-1、MDV-2和疫苗病毒的遗传物质，以显示MDV-2感染和排毒的动力学，以及与MDV-2合并感染的频率。 MDV-1 野毒株和疫苗病毒。我们还将利用数学模型研究 MDV-2 在鸡群内的传播动态。我们将通过对病毒遗传物质进行测序并与已知的 MDV-2 毒株进行比较来确定 MDV-2 毒株的变异性。我们将通过在细胞培养物中培养这些病毒，然后在受控实验室条件下用它们感染鸡来研究 MDV-2 毒株的特征，以检查 MDV-2 的复制、持久性、临床症状和传播。大多数 MDV-2 毒株都具有适合作为 MD 疫苗的特性：它们不会引起疾病，在鸡体内生长良好并持续数月，并且很容易在鸡之间传播，以保持鸡群的高水平暴露。蜂拥而至疫苗病毒。此外，MDV-2可以通过基因工程携带来自其他重要家禽病毒病原体的基因，例如传染性法氏囊病病毒（IBDV）和新城疫病毒（NDV）；像这样的重组“载体疫苗”可以通过单次疫苗接种来保护鸡免受 IBD、ND 和 MD 的感染。我们将设计适当的 MDV-2 毒株来创建“rMDV2-IBD-ND”病毒，然后在受控实验室条件下测试其保护鸡免受这三种疾病的能力。这项研究对于了解广泛传播的 MDV-2 的影响非常重要感染对商业家禽群健康和生产力的影响。一种新的重组 MDV-2 疫苗将成为用于控制 MD 和其他家禽疾病的活病毒疫苗组的有用补充。