Gene structure and diversity analysis of the cattle tick vaccine antigen, TC-X

The cattle tick species Rhipicephalus microplus represents a major ectoparasite within the cattle industry, characterized by its rapid global dispersion, driven by its short life cycle, high reproductive capacity, and ability to adapt to diverse climatic conditions. This species is of considerable global significance due to the substantial economic losses it incurs through increased infestations and the transmission of tick-borne diseases (TBDs), which are associated with elevated morbidity and mortality rates in cattle. Chemical acaricides remain the primary method for tick control; however, their overuse has resulted in resistance across multiple tick species, prompting the exploration of alternative control strategies, such as vaccination. Currently, only one antigen, Bm86, has been commercialized for tick vaccination. Nevertheless, the efficacy of Bm86-based vaccines is geographically variable and necessitates multiple booster immunizations per season, underscoring the need to identify additional protective antigens and develop vaccines that provide long-term immunity. Our research has identified TC-X, a Kunitz protein from R. microplus, as a potential protective antigen in cattle vaccine trials. The combination of TC-X with a second antigen (Antigen 1) has been shown to induce immune memory and elicit a tick-mediated enhancement of the immune response in cattle. However, the gene structure, phylogeny, function, and diversity of TC-X remain poorly understood. In this study, we delineate the gene structure of TC-X, propose its potential roles in tick development and feeding, and demonstrate that the epitope regions predicted from TC-X exhibit low diversity, particularly within Kunitz domain 1. Furthermore, we suggest that TC-X may offer cross-protective benefits against other Rhipicephalus species, as it shares substantial protein identity with homologous proteins in these species. Future research will focus on expanding our RNA sequencing database to explore the global diversity of TC-X further. Ultimately, integrating vaccination strategies with acaricide treatment may reduce tick burdens, mitigate tick-borne diseases, and lessen environmental impacts, providing significant economic benefits to livestock producers.