Novel multivalent vaccines for avian health

H5N1流感病毒最近在禽类中被“重新发现”，特别是在东南亚，并在最近的新闻报道和无数社论中被广泛强调为鸡等禽类的一个主要问题，并作为对人类健康构成重大全球风险的下一次流感大流行的潜在来源。禽流感病毒和其他病毒病原体的其他毒株也引起了家禽业的关注。因此，迫切需要更新更有效的疫苗，通常针对一系列微生物疾病，不仅要保护家禽群，而且要减少向家禽工人及其他人传播的风险。此外，疫苗的设计需要考虑到将自然感染某种微生物的鸟类与接种过这种微生物疫苗的鸟类区分开来。该建议涉及家禽（和其他）疫苗开发中的所有三个问题；这些疫苗1)有效（例如，刺激保护性免疫反应），2)本质上是多价的（一种疫苗配方可用于接种一系列微生物疾病），3)允许将自然感染的鸟类与接种疫苗的鸟类区分开来（DIVA）。在本提案中，我们将利用禽腺病毒9 （FAdV-9）这一无毒性和无症状的病毒作为疫苗载体，并将其设计为一种货物系统，提供几种抗原，以刺激对各种不同禽病毒性疾病的免疫。特别是，我们将确定病毒基因组中在细胞培养中生长所必需的区域，这些区域可以被其他病毒的免疫刺激抗原基因所取代。最初，我们将针对流感病毒的血凝素(H)基因和新城疫病病毒（NDV）的血凝素-神经氨酸酶（HN）基因的结合，这是任何家禽经营中的一个主要问题。我们预计，以FAdV-9为基础的疫苗接种禽类将提供对所有三种病毒性疾病的保护，并（取决于货物的大小）提供更多的微生物剂。保护鸟类免受流感病毒的侵害，不仅可以改善鸟类的健康和生产力，而且还可以通过减少禽流感病毒在禽类向人类传播的发生率，对食品安全产生影响。

Influenza virus H5N1 has recently been "rediscovered" in birds particularly in south east Asia and has been extensively highlighted in recent news reports and countless editorials as a major problem in avian species like chickens and as a potential source for the next flu pandemic posing a major global risk to human health. Other strains of avian influenza virus and other viral pathogens are also a concern to the  poultry industry. Thus there is a dire need for newer more effective vaccines, often to a suite of microbial diseases for not only protection of poultry flocks but also to reduce the risk of spread to poultry workers and beyond. Moreover vaccines need to be designed to allow for differentiation of birds naturally infected by a certain microbe from those that have been vaccinated against it. This proposal addresses all three issues in vaccine development for poultry (and other) vaccines; vaccines that 1) are effective (e.g., stimulate a protective immune respose), 2) are multivalent in nature (one vaccine formulation can be used to vaccinate against a panel of microbial diseases) and 3) allow for the differentiation of naturally infected from vaccinated birds (DIVA). In this proposal we will capitalize on one avian virus, fowl adenovirus 9 (FAdV-9) which is avirulent and asymptomic as a vaccine vector and design it to act as a cargo system to deliver several antigens for stimulation of immunity against a variety of different avian viral diseases. In particular we will identify regions of the viral genome which are dispensible for growth in cell culture and can be replaced by genes for immune stimulating antigens of other viruses. Initially we will target incorporation of the haemagglutinin (H) gene of influenza virus and the haemagglutinin-neuraminindase (HN) gene of Newcastle disease virus (NDV), a major problem in any poultry operation. We expect that vaccination of birds with the FAdV-9 based vaccines will afford protection against all three viral diseases and (depending on how big the cargo can be) even more microbial agents. Protection of birds against influenza viruses will not only improve avian health and productivity, but also impacts on food safety by reducing the incidence of bird to human spread of influenza virus.