Avian Influenza Vaccines for Pandemic Preparedness

描述（由申请人提供）：我们的长期目标是生成准备或预防大流行性流感病毒出现所需的信息。特别令人关切的是，H5N1亚型禽流感（Al）病毒可能会导致大流行。H5N1病毒在几个亚洲国家的家禽中流行，通过从家禽传染给人类，造成了惊人的死亡人数。根除、检疫和疫苗接种政策未能成功地遏制这一疾病，该病毒仍然是一个无所不在的大流行威胁。有两种机制促使H5N1病毒在亚洲长期存在：它们适应多种动物物种的可塑性，并与其他流感病毒一起重新流行，以及它们不断的地理扩张。报告H5N1高致病性禽流感爆发的国家名单继续增加，尽管亚洲有1.6亿只家禽死亡或被扑杀以控制疾病的传播。亚洲家禽业的经济损失估计约为100亿美元，威胁到数百万人的生计。这场前所未有的高致病性禽流感爆发出现了新的转折，已经蔓延到迁徙的野生水禽，可能将病毒传播到世界其他地区，包括北美。这种情况要求制定干预战略，以制止这些病毒的传播。该R21提案的目标是基于以下假设：通过操纵Al病毒的基因组，可以制备活减毒疫苗，其不仅可用于人类的大流行准备，而且可用于动物的疾病控制。我们的疫苗方法将允许易于管理，大规模接种减毒活病毒，并区分接种疫苗和受感染的鸟类，最终将有效控制疾病的传播。

DESCRIPTION (provided by applicant): Our long-term goal is to generate the information needed to prepare for or prevent the emergence of pandemic influenza viruses. There is particular concern about the possibility that avian influenza (Al) viruses of the H5N1 subtype could cause a pandemic. H5N1 viruses, endemic in domestic poultry in several Asian countries, have caused an alarming number of deaths by crossing from poultry to humans. Eradication, quarantine and vaccination policies have not succeeded in containing the disease, and the virus continues to be an omnipresent pandemic threat. Two mechanisms are contributing to the perpetuation of H5N1 viruses in Asia: their malleability to adapt to multiple animal species and reassert with other influenza viruses and their constant geographic expansion. The list of countries reporting outbreaks of H5N1 HPAI continues to increase despite the 160 million domestic poultry that have died or been culled in Asia to control the spread of the disease. The estimated economic losses to the Asian poultry sector are around $10 billion, threatening the livelihood of millions of people. This unprecedented outbreak of highly pathogenic avian influenza has taken a new twist having spread to migratory wild aquatic birds that could spread the virus to other parts of the world, including North America. This situation requires the development of intervention strategies that could bring the spread of these viruses to a halt. The goal of this R21 proposal is based on the hypothesis that by manipulating the genome of Al viruses, live attenuated vaccines can be prepared that will not only be useful for pandemic preparedness in humans but also for the control of the disease in animals. Our vaccine approach will allow ease of administration, mass vaccination of live attenuated viruses, and discrimination of vaccinated from infected birds, which ultimately will effectively control the spread of the disease.