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主要问题，并成为下一次流感大流行的潜在来源，对人类健康构成重大威胁。其他禽流感病毒株和其他病毒病原体也是中国家禽业关注的问题。因此，迫切需要更新、更有效的疫苗，通常是针对一系列微生物疾病，以不仅保护家禽群，而且减少传播给家禽工作者和其他人的风险。此外，疫苗的设计需要将自然感染某种微生物的禽类与接种过疫苗的禽类区分开来。这一建议解决了家禽(和其他)疫苗开发中的所有三个问题；1)有效的疫苗(例如，刺激保护性免疫反应)，2)多价的疫苗(一种疫苗配方可用于接种一组微生物疾病的疫苗)，以及3)允许区分自然感染和接种的禽类(DIVA)。在这项建议中，我们将利用一种无毒和无症状的禽腺病毒9(FAdV-9)作为疫苗载体，并将其设计为一个运输系统，用于运送几种抗原，以刺激对各种不同禽类病毒疾病的免疫。特别是，我们将确定病毒基因组中可用于细胞培养生长的区域，并可被其他病毒的免疫刺激抗原基因所取代。首先，我们的目标是整合流感病毒的血凝素(H)基因和新城疫病毒(NDV)的血凝素神经氨酸酶(HN)基因，这是任何家禽操作中的主要问题。我们预计，用基于FAdV-9的疫苗接种禽类将提供对所有三种病毒疾病的保护，并(取决于货物的大小)甚至更多的微生物制剂。保护禽鸟免受流感病毒侵袭，不仅可以改善禽鸟的健康和生产力，还可以减少禽流感病毒在禽类向人类传播的几率，从而影响食品安全。

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.