ANIHWA call 1: MADISUP. Marek's Disease Virus induced immunosuppression: From diagnosis to vaccination

Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes high economic losses in poultry production. Beside acute death or extensive tumor formation, MDV induces immunosuppression (IS) thus increasing the susceptibility of chickens to other pathogens. Besides being an issue of animal health and welfare, it increases the need for pharmacological treatment and also for the frequency of vaccination against multitude of pathogens, as MDV infection was shown to strongly reduce vaccine responses. Furthermore, MDV vaccines themselves induce mild IS, as such causing a dilemma between the absolute necessity of a MDV vaccination and the reduced response to other vaccines.
Though the phenomenon of IS has been recognised for decades, very little is known about the mechanisms behind MDV-induced IS to date. Our goal is to apply the unique expertise and the techniques developed over the last years by the consortium on MDV and chicken immunology to identify the basic mechanisms associated with IS, and to develop novel MDV vaccines with significantly reduced immunosuppressive properties.

Though the phenomenon of immunosuppression (IS) has been recognised for decades, very little is known about the mechanisms behind MDV-induced IS to date. In this project, we aim to examine the basis of IS in MD infection. Evaluation of MDV-induced IS is currently restricted
to the measurement of thymus and bursa atrophy, a gross and inaccurate method, which can only be performed post-mortem. Therefore, there is a definite need for establishing novel diagnostic tools that facilitate a quantitation of immunosuppressive effects that can be applied to a large scale in poultry production. In the differnt workpackages, we will examine (1) the modulation of the innate and adaptive immune system by evaluating the role of NK cells, and by studying the differential leukogram profiles, (2) role of lymphocyte death as a cause of IS, (3) dynamics of interactions of vaccine viruses in the avian embryo, and finally (4) opportunities of evaluating novel vaccine candidates that do not induce immunosuppression.

By targeting virus-induced immunosuppression, our project aims at understanding the mechanisms. A better knowledge of the immunossuppressive effects of the virus help in devising methods/strategies for preventing losses from the disease. A vaccine that would have reduced immunosuppressive effects will have immense potential in preventing losses and reducing losses and improving welfare. The proposed research will benefit the poultry industry as an improved understanding of the molecular mechanisms of MDV immunosuppression could lead to new strategies of control. Judging from the interest in the lay press, there is a considerable interest among the public for the scientific understanding of how some diseases produce damage to animal health. What will be done to ensure that they have the opportunity to benefit from this research? A special attention will be paid to the exploitation of results as this project will identify genes, molecular and cellular mechanisms which may be at the origin of industrial developments. A consortium agreement will be engaged and negotiated through the institutional representative of each partner. Material rights may concern cell-lines or vaccines which may arise as breakthrough developments from WP1 - 2 and 4. The project aims mainly to target the poultry vaccine market with a promising new offer in MDV replication process that can be monitored in vitro and therefore that can lead to a better production and control of the poultry vaccines.