Combating Swine Influenza Initiative (model project)

抗击猪流感倡议（示范项目）

• 批准号: BB/H014292/1
• 负责人: Ian Brown
• 金额: $ 85.62万
• 依托单位: ANIMAL AND PLANT HEALTH AGENCY
• 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%2FH014292%2F1
• 关键词: Combating; Swine; Influenza; Initiative; model

The first human influenza pandemic in more than 30 years is ongoing, with the causative virus having arisen from the combination of two different swine influenza viruses, one originating in the USA and the other in Europe. Analyses have demonstrated that the two progenitor viruses were circulating undetected, probably in pigs, for around 9 years. The ability of influenza viruses to both combine with each other to produce new viruses and also to mutate rapidly are important features in their ability to transmit in novel mammalian species, including humans. Pigs are susceptible to a larger range of influenza viruses than most other animals and this makes them of importance as animals in which such viral mixing can happen. Swine flu infection is common in pigs in Europe and circulates through many farms on at least an annual basis. Experimental studies at VLA have demonstrated that pigs can be infected with the pandemic human virus and, importantly, can spread the virus to other pigs that they are co-housed with. Outbreaks of swine flu in pigs, caused by the human pandemic virus, have occurred in at least three countries, probably following infection of pig farmers who have transmitted the virus to pigs. In Great Britain, some pigs are farmed in large, very dense populations and, should these farms become infected with the pandemic flu virus, large amounts of virus would be produced with unpredictable consequences for the farmers caring for the pigs. The origin of the human pandemic virus from swine flu viruses, the susceptibility of pigs to the pandemic virus and the infection of pig farms around the world, against the background of their potential 'mixing vessel' role, raises several immediate and important questions and challenges for both human and swine health. This grant, along with the parallel population grant application, aims to answer some of them and, in doing so, to provide an immediate scientific evidence base to inform policies aimed at minimising the impact of the pandemic in both humans and animals. We will define the consequences of spread of the pandemic virus to pigs, considering the individual clinical presentation, including the host or 'patient' mechanisms that result in disease signs, and the transmission of the virus. These studies will take into account that some pigs may be naturally partially immune through prior 'normal' swine flu infection. We will use this work to estimate the likely challenge posed to public health by pig infection with the pandemic virus. Our detailed investigations will include genetic studies of swine influenza, immunological and virological studies of infection of pigs with the 'normal' swine and pandemic strains of the virus. We will study the level of transmission of the virus from pig to pig and investigate the clinical impact of the disease. This project will substantially add to the amount of data available on swine influenza so that we can properly estimate how much future risk is posed by this infection. Through comparing data from the pig studies and that derived from human cases occurring as the pandemic virus spreads we will be able to evaluate the pig as an animal model for suitability to studying pandemic influenza consequences for humans. The data generated from this grant will be used to study the rates of viral mutation and identify the specific mutations in influenza viruses that are associated with spread between pigs and people working with pigs. This will enable us to better predict the immediate threats from the pandemic virus mutating to become more virulent in people and pigs, particularly if the human pandemic virus becomes endemic in the pig population.

30多年来，人类流感大流行正在进行中，由于两种不同的猪流感病毒的结合而产生了病毒，一种病毒源于美国，另一种源自美国，另一种源自欧洲。分析表明，这两个祖先病毒在大约9年的时间内未发现，可能在猪中循环。流感病毒彼此结合以产生新病毒的能力以及快速突变的能力是它们在包括人类在内的新型哺乳动物物种中传播的能力。猪比大多数其他动物都容易受到更多的流感病毒的影响，这使它们成为可能发生这种病毒混合的动物。猪流感感染在欧洲的猪中很常见，并且至少每年通过许多农场循环。 VLA的实验研究表明，猪可以感染大流行的人类病毒，重要的是，可以将病毒传播到与他们共同居住的其他猪。由人类大流行病毒引起的猪流感爆发发生在至少三个国家，可能是在感染已将病毒传播给猪的养猪者感染之后。在大不列颠，一些猪被大量的人群耕种，如果这些农场感染了大流行流感病毒，将会产生大量病毒，并对照顾猪的农民产生不可预测的后果。猪流感病毒的人类大流行病毒的起源，猪对大流行病毒的敏感性以及世界各地的养猪场感染，在其潜在的“混合容器”角色的背景下，对人类和猪健康提出了几种直接而重要的问题和挑战。这笔赠款以及平行的人口赠款的应用程序旨在回答其中的一些资金，并为此提供直接的科学证据基础，以告知旨在最大程度地减少大流行对人类和动物的影响的政策。我们将考虑各个临床表现，包括导致疾病症状的宿主或“患者”机制，以及病毒的传播，定义大流行病毒向猪传播的后果。这些研究将考虑到某些猪通过先前的“正常”猪感染自然可以部分免疫。我们将利用这项工作来估计猪感染大流行病毒对公共卫生构成的挑战。我们的详细研究将包括对猪流感的遗传研究，具有“正常”猪的猪感染的免疫学和病毒学研究。我们将研究病毒从猪到猪的传播水平，并研究疾病的临床影响。该项目将大大增加猪流感上可用的数据量，以便我们可以正确估计这种感染带来了多少未来风险。通过比较猪研究的数据，并从人类病例中得出的数据随着大流行病毒的扩散而得出，我们将能够评估猪作为动物模型，以适合研究对人类的大流行性流感后果。该赠款产生的数据将用于研究病毒突变的速率，并确定与猪与猪工作人员之间的传播相关的流感病毒中的特定突变。这将使我们能够更好地预测大流行病毒突变的直接威胁在人和猪中变得更加强大，尤其是如果人类大流行病毒在猪群中流行时。

项目成果

A gene expression atlas of the domestic pig.

• DOI: 10.1186/1741-7007-10-90
• 发表时间: 2012-11-15
• 期刊: BMC biology
• 影响因子: 5.4
• 作者: Freeman TC;Ivens A;Baillie JK;Beraldi D;Barnett MW;Dorward D;Downing A;Fairbairn L;Kapetanovic R;Raza S;Tomoiu A;Alberio R;Wu C;Su AI;Summers KM;Tuggle CK;Archibald AL;Hume DA
• 通讯作者: Hume DA

Immune responses in pigs vaccinated with adjuvanted and non-adjuvanted A(H1N1)pdm/09 influenza vaccines used in human immunization programmes.

• DOI: 10.1371/journal.pone.0032400
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Lefevre EA;Carr BV;Inman CF;Prentice H;Brown IH;Brookes SM;Garcon F;Hill ML;Iqbal M;Elderfield RA;Barclay WS;Gubbins S;Bailey M;Charleston B;COSI
• 通讯作者: COSI