Strategies for developing multi-epitope subunit vaccines against tick-borne protozoa and bacteria

The emergence of tick-borne protozoa and bacteria poses significant threats to both livestock and human health, underscoring the urgent need for effective vaccination strategies. Multi-epitope subunit vaccines offer a promising solution, as they can elicit robust humoral and cellular immune responses. This review synthesizes current knowledge on the development of multi-epitope subunit vaccines against tick-borne protozoan and bacterial pathogens. Advances in immunoinformatics, bioinformatics, molecular biology, and proteomics have enabled the identification of key immunogenic proteins and epitopes in protozoa, including Theileria and Babesia, as well as in bacteria such as Ehrlichia spp., Anaplasma spp., Borrelia burgdorferi sensu lato, Rickettsia prowazekii, and Coxiella burnetii. Building on these findings, the integration of epitope mapping with molecular docking and stability prediction analyses allows rational vaccine design with enhanced potential efficacy. Complementary strategies, including the use of lipid nanoparticles and adjuvants, have been proposed to further improve immune responses. Despite these advances, significant challenges remain, particularly in translating in silico predictions into in vivo protection, ensuring rigorous experimental validation, and understanding mid- to long-term safety. By bringing out these developments and identifying gaps in current knowledge, this review provides a comprehensive perspective on multi-epitope vaccine design and outlines directions for future experimental validation and field application.