Hematophagous arthropods are responsible for the transmission of a variety of pathogens that cause disease in humans and animals. Ticks of the Ixodes ricinus complex are vectors for some of the most frequently occurring human tick-borne diseases, particularly Lyme borreliosis and tick-borne encephalitis virus (TBEV). The search for vaccines against these diseases is ongoing. Efforts during the last few decades have primarily focused on understanding the biology of the transmitted viruses, bacteria and protozoans, with the goal of identifying targets for intervention. Successful vaccines have been developed against TBEV and Lyme borreliosis, although the latter is no longer available for humans. More recently, the focus of intervention has shifted back to where it was initially being studied which is the vector. State of the art technologies are being used for the identification of potential vaccine candidates for anti-tick vaccines that could be used either in humans or animals. The study of the interrelationship between ticks and the pathogens they transmit, including mechanisms of acquisition, persistence and transmission have come to the fore, as this knowledge may lead to the identification of critical elements of the pathogens' life-cycle that could be targeted by vaccines. Here, we review the status of our current knowledge on the triangular relationships between ticks, the pathogens they carry and the mammalian hosts, as well as methods that are being used to identify anti-tick vaccine candidates that can prevent the transmission of tick-borne pathogens.

Amsterdam UMC Location AMC Center for Experimental and Molecular Medicine Amsterdam The Netherlands

Biology Centre Institute of Parasitology Czech Academy of Sciences Branišovská 31 37005 Ceske Budejovice Czech Republic

Centre for Zoonoses and Environmental Microbiology Centre for Infectious Disease Control National Institute for Public Health and the Environment Bilthoven The Netherlands

CIC bioGUNE 48160 Derio Spain

Faculty of Science University of South Bohemia Branišovská 31 37005 Ceske Budejovice Czech Republic

Ikerbasque Basque Foundation for Science 48012 Bilbao Spain

Institute for Parasitology and Tropical Veterinary Medicine Freie Universität Berlin Berlin Germany

Institute of Virology Biomedical Research Center of the Slovak Academy of Sciences Bratislava Slovakia

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