Work Package 6
Assessment of T cells responses against Marek’s disease virus (MDV) infection and vaccination
Marek’s disease virus (MDV) is a highly oncogenic alphaherpesvirus that infects chickens and causes paralysis, immunosuppression and deadly lymphomas. MDV-induced lymphomas are considered to be the most prevalent clinically-diagnosed cancer in animals and the virus causes substantial economic losses in poultry industry worldwide. Even though current MDV vaccines are highly effective in minimizing commercial losses due to tumor formation, they do not elicit sterilizing immunity, allowing a continued evolution of MDV strains in vaccinated chickens. Since the advent of widespread vaccination, MDV field strains have continuously increased in virulence, allowing the virus to overcome vaccine protection. Therefore, we need a better understanding of MDV pathogenesis and vaccine responses in chickens to develop more potent vaccines that control this deadly pathogen.
In the first funding period, we established cutting-edge technologies, including TCR repertoire sequencing, MDV-specific MHC tetramers, and type I and III interferon knockout chickens, that will be used to investigate the immune response against MDV. Using these technologies, we will (i) identify the virus- and vaccine-induced T cell clonotypes induced by MDV infection and vaccination, characterizing their specificity and roles in immunity and tumor control, and (ii) assess how type I and III interferons modulate the adaptive immune responses, and investigate the role of type III interferons in controlling very virulent MDV using the knockout chickens.
By integrating these innovative technologies, we will uncover critical aspects of T cell-mediated immunity, which plays an important role in the protection against MDV as antibodies only delay but not prevent disease. The proposed experiments will not only reveal the TCR clonotypes induced by MDV infection and vaccination and their role in the immune response against MDV, but also how type I and III interferons shape the immune response against this highly oncogenic virus. This highly collaborative project is only possible by interactions with ImmunoChick members and will provide important insights into both Marek’s disease and the chicken immune system.
Principal investigator:
PhD-student:
tba