Abstract
Tick-borne diseases have increased significantly due to several factors, including climate change. Ticks can carry diverse pathogens, and transmission is facilitated by immunosuppressive tick salivary proteins. Vaccination targeting tick salivary proteins has been proposed as a strategy to enhance broad acquired immunity against tick-borne pathogens. Given the immunosuppressive nature of these proteins, we leveraged the ability of nanoparticles to enhance antigen immunogenicity. We synthesized nanoparticles directly from tick salivary proteins, evasin-3 and tick salivary lectin pathway inhibitor (TSLPI), by desolvation with ethanol and cross-linking. Nanoparticles formulated with the CpG oligonucleotide adjuvant significantly enhanced both humoral and cellular immune responses against both evasin-3 and TSLPI in mice compared to soluble CpG adjuvanted antigens. These results demonstrate the importance of antigen delivery and presentation, particularly for poorly immunogenic antigens, and the potential for protein nanoparticles to be developed as vaccines against diverse tick-borne pathogens.