Background Ixodes ricinus transmits bacterial, protozoal and viral pathogens that cause Lyme borreliosis, babesiosis and tick-borne encephalitis respectively and exceedingly affect Central and Eastern Europe (CEE). During feeding, ticks introduce salivary proteins in the skin that interfere with host defense mechanisms. However, in animals repeated tick infestations as well as vaccination against selected tick proteins can lead to decreased pathogen transmission by inhibiting tick feeding - known as ‘tick immunity’ - or by neutralizing tick proteins that facilitate the transmission of tick-borne pathogens (TBPs). Also humans with hypersensitivity to tick-bites have a lower risk of contracting tick-borne diseases (TBDs). Therefore, anti-tick vaccines encompass an innovative strategy to prevent TBDs in humans, or animals and wildlife to indirectly reduce the risk of contracting TBDs for humans.Overall Objective To identify and characterize tick proteins involved in ‘tick immunity’ and TBP transmission and to use this knowledge to develop anti-tick vaccines to prevent multiple human TBDs.Methods Using state of the art proteomic and transcriptomic approaches we will identify and characterize novel tick salivary gland proteins, which will be subsequently assessed as anti-tick vaccines to protect against LB, babesiosis and TBE in animal models. In addition, through an integrated and multidisciplinary approach involving CEE public health institutes, health organizations and industrial companies we will examine how to develop anti-tick vaccines and implement these in public health systems.Impact ANTIDotE will deliver 1) essential knowledge on the biological mechanisms involved in the pathogenesis of TBDs, 2) proof of concept of an anti-tick vaccine protecting against multiple human TBPs and 3) plans for exploitation and implementation of anti-tick vaccines, significantly contributing to downscaling the severe medical and economic burden that TBDs have on societies.