Combating avian influenza through systematic analysis of antigenic drift, genetic variation, and development of novel diagnostic tools and vaccines

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The global poultry industry has shown great promise for increased, cost-effective production of animal protein to meet food security challenges. Poultry production has contributed significantly to economic growth in transitioning the economies of developing nations; it has helped meet goals in poverty alleviation and reduction in rural unemployment, particularly amongst women. However, the emergence and spread of the highly pathogenic avian influenza (HPAI) H5N1, and the widespread endemic presence of low pathogenicity avian influenza (LPAI) subtypes in many countries has threatened the sustainability of the sector through incurring heavy losses in both commercial and backyard poultry production. The rapid genetic evolution and potential reassortment of HPAI and LPAI subtypes in birds remains a credible threat for pandemic emergence. Control of these viruses presents formidable challenges to public health and veterinary infrastructures. Intervention programs require accurate and timely detection of virus subtypes, and typically involve ring culling of at-risk flocks, movement and trade restrictions, and vaccination campaigns. In poor countries, large scale culling has become impractical for economic, ecological and ethical reasons, since the viruses are endemic over wide regions and in multiple diverse avian species. The effectiveness and suitability of currently available diagnostic tools and vaccines is limited by insufficient laboratory capacity, the inherent diversity of wild type circulating viruses, and inadequate vaccine delivery mechanisms. The proposed research will exploit next generation biotechnological approaches to gain new knowledge and improve control strategies to minimize economic losses due to influenza within the poultry sector, and to mitigate the risk of pandemic emergence. We will examine the different epidemiology and ecology of influenza in Vietnam and Pakistan, in relationship to differing levels of industrialization of their poultry sectors, and to provide insight into the different pathways that impact on sustainable control of AIV. These studies will advance our understanding of how genetic and antigenic diversity influences the protective efficacy of vaccines and the sensitivity/specificity of diagnostic technologies. The precise determination of antigenic epitopes critical for induction of protective immunity in chickens and ducks will inform the design of more broadly effective vaccines. These broadly cross-reactive and protective AIV antigens will be integrated into proven viral vaccine vectors; we will engineer duck enteritis virus (DEV) and the herpesvirus of turkeys (HTV) to produce multivalent recombinant live vaccines capable of protecting ducks or chickens against AIV, as well as duck plague and Marek's disease, respectively. These next generation vaccines be delivered through mass vaccination strategies (in ovo) and will allow easy differentiation of infected from vaccinated birds (DIVA). We will develop novel rapid diagnostics to differentiate major AIV subtypes infecting poultry at the pen-side. These technologies have the potential to transform control strategies by empowering farmers to identify infected flocks at an early stage, and the dual protection against highly prevalent economically important diseases (duck plague and Marek's disease) will motivate uptake of the vaccine. Through our community-based study sites, we will explore farmer attitudes and perceptions regarding disease interventions, and assess the impact of novel technologies. The knowledge and improved tailored-made tools for control and management of AIV in Vietnam and Pakistan will reduce production losses and help prevent outbreaks with a high risk of zoonotic infections. In addition to direct benefits to farming communities, the improved control measures may offer substantial indirect economic, public health, environmental and social benefits to wider communities on both the national and global scale.