The Enigma of Identifying New Cattle Tick Vaccine Antigens

Several reviews have summarised cattle tick Rhipicephalus (Boophilus) microplus vaccine candidate discoveries by comparing efficacies and localisation characteristics. However, few have re-analysed all the reported proteins using modern bioinformatics tools. Bm86 was developed as a successful vaccine in the 1980s; however, global efficacies vary from 45 to 100%. Subsequent vaccines, including four published patents, were discovered by targeting enzymes important for blood digestion and/or metabolism or by targeting genes shown to disrupt tick survival following RNA interference experiments. This chapter analyses published vaccine candidates using InterPro, BLASTP, SignalP, TMHMM and PredGPI tools to confirm whether each reported protein is likely to be secreted, membrane associated or intracellular. Conversely, these proteins are considered as ‘exposed’, ‘exposed’ and ‘concealed’ or ‘concealed’, respectively. Bm86 was always described as a ‘concealed’ antigen; however, the protein has a confirmed signal peptide and GPI anchor which suggests it is anchored to the cell membrane and exposed on the surface of gut cells. It is the only tick vaccine with a GPI anchor. Secreted vaccine candidates appear to have promise and exhibit higher efficacies if delivered with an ‘intracellular’/‘concealed’ antigen. Improvements in tick genomics and bovine immunomic resources will assist to identify robust new cattle tick vaccines.