AbstractEpstein-Barr virus (EBV) is one of the most common human viruses and the cause of pathologies such as infectious mononucleosis (IM) and certain cancers. No vaccine against EBV infection currently exists, but such vaccines are in development. Knowledge of how EBV is transmitted at the population level is critical to the development of target product profiles (TPPs) for such vaccines and future vaccination strategies. We present the first mathematical model of EBV transmission, parameterised using data from England, and use it to compare hypothetical prophylactic vaccines with different characteristics and the impact of vaccinating different age groups. We found that vaccine duration had more impact than vaccine efficacy on modelled EBV and IM prevalence. The age group vaccinated also had an important effect: vaccinating at a younger age led to a greater reduction in seroprevalence but an increase in IM cases associated with delayed infection. Vaccination had impact on cancer incidence only in the long run, because in England most EBV-related cancers arise in later life. Durability of protection should be a key factor to prioritise in EBV vaccine development and included in vaccine TPPs. These findings are timely and important for vaccine developers and policy-makers alike.