Novel multivalent vaccines for avian health

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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.