Anti-tick and Borrelia-targeted vaccines: Target discovery and vaccine platforms

Next to mosquito’s, ticks are the most important vectors of human and veterinary disease worldwide. However, there are only vaccines available for a few tick-borne diseases. A vaccine that could block tick feeding and subsequent pathogen transmission could greatly benefit human and veterinary health.
This thesis aimed to identify tick antigens for such an anti-tick vaccine. In the first part an in vitro tick feeding assay was developed to be able to assess the effect vaccination with Rhipicephalus antigens in vitro, and used to assess the effect of known tick antigens.
In the second part, anti-tick vaccine candidates from Ixodes ticks and the transmission of the causative agent of Lyme borreliosis were investigated. It was shown that vaccination with homologues of Bm86 - the basis for a vaccine against Rhipicephalus ticks - does not affect feeding of I. ricinus ticks. Therefore, our quest for novel vaccine candidates in Ixodes tick saliva continued. Firstly, using a transcriptomic approach multiple tick salivary gland proteins (TSGPs) were shown to be upregulated during tick feeding in Borrelia-infected ticks and tested as vaccine antigens. Secondly, a Yeast Surface Display containing Ixodes TSGPs was created and multiple immunoscreenings were performed to identify conserved immunogenic TSGPs in rabbits or humans. Vaccination with selected tick antigens resulted in impaired tick feeding. Lastly, DNA vaccination was assessed as an alternative vaccine platform/for novel anti-tick vaccines.
Collectively, this thesis provided tools and insights aiding in the development of vaccination strategies targeting the tick to prevent tick-borne diseases.