Combating highly pathogenic avian influenza: Novel vaccination strategies using recombinant live avian viral vaccine vectors

对抗高致病性禽流感：利用重组活禽病毒疫苗载体的新型疫苗接种策略。禽流感病毒（或通常称为“禽流感”）自然存在于水禽和滨鸟等野生鸟类中，这些鸟类的病毒种类繁多，通常不具有致病性。这些低致病性禽流感（LPAI）病毒通常从野鸟宿主传播并感染家禽，经常成为高致病性病毒（HPAI），这对商业家禽极其危险，有时对人类致命。在包括欧盟在内的世界许多地区最近爆发的H5和H7亚型高致病性禽流感病毒中，超过2亿只家禽死亡或被扑杀，造成巨大的社会经济成本。目前起源于东南亚并最近通过候鸟远距离传播的高致病性H5N1流行病是前所未有的。候鸟对英国和其他欧盟国家构成的风险程度尚不清楚，然而，越来越多的证据（最近在苏格兰法夫岛有候鸟死于H5N1）表明，在家禽和其他笼养鸟类中预防和控制禽流感疾病爆发将是未来许多年的一项重大挑战。迄今为止，在英国和其他一些国家控制家禽高致病性禽流感的主要战略是通过大规模扑杀感染和接触禽群来消灭病毒。然而，目前这一世界性流行病严重影响了发达国家和发展中国家的经济。因此，出于伦理、生态和经济的原因，主要通过大规模屠杀动物来控制和根除人工智能已不再被认为是可以接受的。因此，欧洲议会、世界动物卫生组织（兽疫局）和粮食及农业组织（粮农组织）不仅允许在疾病爆发后进行紧急疫苗接种，而且还允许将预防性疫苗接种作为控制人工智能的额外工具。目前，可用的禽流感灭活疫苗是在胚胎卵中生产的，有几个缺点。我们建议使用一些最先进的生物技术工具开发新型疫苗。这将允许在孵化时或孵化前将活病毒疫苗单次注射到鸡蛋中（在蛋疫苗接种中）。这些新的改良疫苗将是安全、有效和经济的，最重要的是保护商品家禽和其他家禽免受禽流感病毒的疾病和传播，从而防止禽流感病毒传播，避免迫在眉睫的全球大流行威胁。

Combating highly pathogenic avian influenza: Novel vaccination strategies using recombinant live avian viral vaccine vectors. Avian influenza (AI) viruses (or the 'avian flu' as it is commonly called) naturally exist in wild birds such as waterfowl and shore birds where the virus is highly diverse and generally not pathogenic. These low pathogenic avian influenza (LPAI) viruses routinely cross over from the wild-bird reservoir and infect domestic poultry, frequently becoming highly pathogenic viruses (HPAI), which are extremely dangerous to commercial poultry and are occasionally fatal to humans. In the recent outbreaks of HPAI viruses of H5 and H7 subtypes in many parts of the world, including the EU, more than 200 million domestic poultry have either died or been culled, impecting huge socio-economic costs. The current epidemic of HPAI H5N1 originating from south East Asia and recently transmitted over long distances via migratory birds is unprecedented. The magnitude of risk that migratory birds are posing to the United Kingdom and other EU countries is not clear, however, there is growing evidence (recent death of migratory swan by H5N1 in Fife, Scotland) suggesting that the prevention and control of AI disease outbreak in poultry and other captive birds will be a major challenge for many years to come. To date the main strategy for controlling HPAI in domestic poultry in UK and in some other countries has been eradication of the virus by large scale culling of infected and contact flocks. However, the current world-wide epidemic has severely affected the economies of developed as well as developing countries. Therefore, for ethical, ecological and economic reasons, it is no longer considered acceptable to control and eradicate AI mainly by the mass killing of animals. As a result the European Parliament, the World Organization for Animal Health (OIE) and Food and Agriculture Organization (FAO) have allowed not only emergency vaccination, following disease outbreak, but also preventive vaccination as an additional tools for the control of AI. Currently, the available AI inactivated vaccines are produced in embryonated eggs and have several disadvantages. We propose to develop novel vaccines using some of the state of the art biotechnological tools. These will allow the administration of live viral vaccines as single injection either at hatch or into eggs before they hatch (in ovo vaccination). These new improved vaccines will be safe, effective and economical, and above all protect the commercial poultry and other domestic birds from disease and dissemination of AI viruses into the environment, consequently preventing AI virus spread, averting the looming global pandemic threat.