Tu145 - Characterisation of the Immune Response to EBV Infection in Tonsil Organoid Cultures

Abstract Text: Despite the global health and economic problems that Epstein Barr Virus (EBV) poses, there is no licensed prophylactic vaccine. A better understanding of protective immunity against EBV would be easier if more were known about the immunological and virological events that occur during primary infection. However, for obvious reasons, we are almost completely ignorant about the earliest phases of the virus-host interaction. Since the initial phases of both EBV infection, and the immune response to EBV occur in the oropharynx where tonsils are located, we have undertaken a high-resolution study of the very first phases of virus infection and the immune response to that infection using a physiologically relevant model: EBV infection of tonsil organoids. Strikingly, EBV replication is efficiently controlled in tonsillar tissue from seropositive children , whereas EBV transformed cells are readily isolated after infection of tonsils from seronegative subjects. We have analysed the humoral, cellular and cytokine/chemokine responses in these organotypic cultures and characterised key features influencing control or susceptibility to EBV infection of B cells in these cultures. The implications of this work for vaccine development will be discussed.