Understanding influenza A virus: linking transmission, evolutionary dynamics, pathogenesis and immunity in pigs

由于人畜共患传染病导致人类大流行的威胁，猪流感引起了相当大的关注。在大流行期间，由于担心从猪身上产生的病毒可能会感染人，导致一些国家的动物遭到广泛破坏，并颁布了贸易禁令。因此，这种高度流行的病毒对猪群健康和福利的潜在影响，估计会使每头成品猪的生产成本增加7 GB，没有得到应有的重视。流感病毒引起的原发病通常较轻，但导致较易发生二次感染。接种疫苗将是控制猪流感的关键措施，以改善猪群健康。通过我们的研究，我们将更详细地了解病毒传播的动力学，以及传播和接种疫苗在推动病毒进化方面的后果。在这些研究期间，我们还将确定一系列参数，例如局部和全身免疫反应以及病毒复制地点，这些参数与传播的开始和停止有关。我们需要知道，目前和正在开发的新型疫苗是否不仅能防止临床症状，还能防止病毒在不知不觉中传播。此外，如果病毒可以在不被注意的情况下传播，它们是否会因为人群中的免疫反应而发生变化？要回答这些问题，我们需要详细了解病毒的传播，以及病毒在动物之间传播时如何变化。然后，我们可以将这一新知识应用于疾病传播的人口范围模型，以预测任何拟议的控制措施的效率。这一知识也将为新型疫苗的设计提供依据。在欧洲，猪流感疫苗接种并不是常规的，主要有两个原因：疫苗接种的成本效益尚未得到明确证明，以及现有疫苗是否能预防目前在猪群中传播的病毒株。后者最显著的例子是，目前的疫苗不包括大流行性H1N1流感病毒抗原。这些研究将为设计猪流感控制程序提供必要的证据，最显著的是：i)找出目前控制感染传播的预防方法的有效性；ii)人群中需要什么水平的免疫来防止感染的传播和新毒株的进化；iii)确定新的、广泛交叉保护的疫苗是否在控制猪流感感染方面更有效，以促进动物健康和牲畜生产。重要的是，这类信息不适用于任何携带流感病毒的天然哺乳动物，包括人和马。因此，我们的研究结果将对流感控制措施产生广泛影响。

Swine influenza attracts considerable attention because of the threat of zoonotic infections causing human pandemics. During the pandemic, a fear that viruses emerging from pigs may infect people resulted in the widespread destruction of animals in some countries and trade bans. Consequently, the insidious effects of this highly prevalent virus on the health and welfare of pig populations, estimated to increase the cost of production by £7 per finished pig, have not been given due regard. The primary disease caused by influenza virus in usually mild, but results in greater susceptibility to secondary infections. Vaccination will be a key control measure for influenza in pigs to improve general herd health.Through our studies we will develop a more detailed understanding of the dynamics of virus transmission and the consequences of transmission and vaccination in driving viral evolution. During these studies we will also define a range of parameters, for example local and systemic immune responses and sites of virus replication, which are associated with the onset and cessation of transmission. We need to know if current and proposed novel vaccines not only prevent clinical signs but also stop viruses being transmitted unnoticed. Furthermore, if viruses can be transmitted unnoticed are they changing because of the immune response in the population? To answer these questions we need to understand virus transmission in detail and how the viruses change when they pass between animals. We can then apply this new knowledge to population wide models of disease spread to predict the efficiency of any proposed control measures. This knowledge will also inform the design of novel vaccines.Vaccination against influenza in pigs is not routinely performed in Europe mainly for two reasons: the cost benefit of vaccination has not been clearly demonstrated and it is not clear that the available vaccines will protect against the strains currently circulating in the pig population. The most striking example of the latter is that current vaccines do not include pandemic H1N1 influenza virus antigen.These studies will provide essential evidence to design control programmes for influenza in pigs, most notably: i) finding out how efficient are the current prophylactic methods at controlling the spread of infection; ii) what level of immunity is required in a population to prevent the spread of infection and the evolution of new strains of virus and iii) determine whether new, broadly cross protective vaccines are more effective at controlling influenza infections in swine to enhance animal health and livestock production.Importantly, this type of information is not available for any natural mammalian hosts of influenza viruses, including humans and horses. Therefore, the results of our studies will have a broad impact on influenza control measures.