Novel multivalent vaccines for avian health

流感病毒H5 N1最近在鸟类中被“重新发现”，特别是在东南亚，并且在最近的新闻报道和无数社论中被广泛强调为禽类物种如鸡的主要问题，并且作为下一次流感大流行的潜在来源，对人类健康构成重大的全球风险。其他禽流感病毒株和其他病毒病原体也是家禽业关注的问题。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，不仅用于保护家禽群，而且还用于降低传播给家禽工人和其他人的风险。此外，疫苗需要设计成允许将被某种微生物自然感染的鸟类与已经接种过该微生物的鸟类区分开。该提议解决了家禽（和其他）疫苗的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）本质上是多价的（一种疫苗制剂可用于针对一组微生物疾病进行疫苗接种）和3）允许区分自然感染的禽和接种疫苗的禽（DIVA）。在这个提议中，我们将利用一种禽病毒，禽腺病毒9（FAdV-9），这是无毒和无症状的疫苗载体，并设计它作为一个货物系统，以提供几种抗原刺激免疫对各种不同的禽病毒性疾病。特别地，我们将鉴定病毒基因组中对于细胞培养物中的生长是必需的并且可以被其他病毒的免疫刺激抗原的基因所取代的区域。最初，我们将针对流感病毒的血凝素（H）基因和纽卡斯尔病病毒（NDV）的血凝素-神经氨酸酶（HN）基因的整合，这是任何家禽经营中的一个主要问题。我们预计用基于FAdV-9的疫苗接种禽类将提供针对所有三种病毒性疾病的保护，并且（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感染，不但可改善禽鸟的健康和生产力，亦可减少禽流感病毒由禽鸟传播至人类的机会，从而影响食物安全。

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.