Bovine and tick responses towards vaccination with Bm86 and its putative binding partners

Abstract

Rhipicephalus microplus and its associated diseases affect ~80% of the world’s cattle population, with a staggering financial impact, especially in developing countries. Despite the vast amount of research dedicated to tick vaccine development, there is only one commercial success, namely the Bm86-based vaccines. The efficacy of Bm86-based vaccines varies across different geographical areas, encouraging the development of improved vaccines. In this study we followed a novel and systematic approach to improve the efficacy of Bm86, the only antigen used in commercialised vaccine formulations against R. microplus. By means of a yeast two-hybrid approach we validated several protein-protein interactions of Bm86 and BmATAQ, respectively, previously identified by our research group. To improve the efficacy of the current Bm86-based vaccine we formulated a combinatorial vaccine in an attempt to target a complex of proteins possibly involved in the same biological pathway. Bm86 and its putative interacting proteins were evaluated in different combinations with some yielding significant results. The transcriptomic response of midgut tissue from R. microplus that fed on Bos taurus cattle vaccinated with Bm86 and its putative binding protein, KUBP was assessed. This allowed for the first time to identify differentially regulated transcripts, giving substantial insight into the mechanism by which the tick counteracts current stress from the immune response elicited by cattle upon vaccination. This research entailed a novel systematic approach that used a combination of in vivo vaccine cattle trials together with functional genomic techniques, permitting the prediction of putative antigens that would enhance vaccine formulation. To date, there is no vaccine available against ticks in South Africa. The development of a vaccine would lessen the pressure on ticks to evolve resistance to acaricides and would also lessen environmental contamination and economic losses brought on by R. microplus.