Immunization with mRNA-LNPs Encoding Ornithodoros Argasid Tick Antigens Induces Humoral Immune Responses and Tick Resistance.

Argasid ticks Ornithodoros erraticus and Ornithodoros moubata are major vectors of zoonotic pathogens, including the African swine fever virus and relapsing fever Borrelia spp., and their control is essential to reduce disease transmission. In this study, we evaluated the immunogenicity and protective efficacy of four Ornithodoros tick antigens formulated as mRNA-lipid nanoparticles (mRNA-LNPs): OeSOD, OeTSP1, OmPLA2, and Om86. Rabbits were immunised with three doses of each mRNA-LNP construct, and immune responses and tick biological parameters were assessed following infestation with both tick species. All mRNA-LNP constructs induced antigen-specific IgG responses that recognised native proteins in tick saliva and midgut extracts. Vaccination resulted in significant reductions in female oviposition and fertility, which correlated with antibody levels, and yielded protective efficacies of 21.9-41.6% against O. moubata and 23.1-41.6% against O. erraticus. Notably, the mRNA-LNPs of OeSOD and OeTSP1 outperformed their recombinant counterparts against O. moubata, and Om86 mRNA-LNP conferred markedly improved protection against both O. moubata and O. erraticus. These findings highlight the potential of mRNA-LNP vaccines to induce effective anti-argasid tick immunity and provide a promising platform for the development of sustainable strategies to control argasid ticks and associated pathogens.