A Multivalent mRNA Vaccine to Prevent Transmission of Tick-bornePathogens

ABSTRACT This Phase I proposal seeks to improve a novel vaccine for human use against pathogens transmitted by the blacklegged tick, Ixodes scapularis. In previous studies, we proposed that vaccine targeting of tick salivary proteins (Salps) critical for tick feeding would impair tick feeding and consequently thwart the transmission of multiple tick-borne pathogens. Our hypothesis is validated by the phenomenon of acquired tick-resistance wherein, upon repeated tick infestations non-natural hosts such as rabbits, and guinea pigs mount a robust immune response against tick Salps critical for tick feeding and this results in rapid rejection of ticks and also prevents transmission of B. burgdorferi. Exploiting this phenomenon, we identified several Salps that are avidly recognized by tick-resistant animal sera. Previous studies have successfully defined a 19Salp-mRNA (19ISP) cocktail that impairs tick feeding, reduces tick engorgement, and blocks transmission of B. burgdorferi. These results are now published in the journal Science Translational Medicine (Sajid et al, 2021, 13, eajb9827). Further experiments showed that a 12 mRNA-LNP subset is sufficient to prevent tick feeding. However, erythema at the tick bite site in immunized animals raises issues with the safety and commercial success of this experimental vaccine. In preliminary experiments we have demonstrated that erythema is not sufficient to provoke tick rejection. In this proposal we will further refine the antigen cocktail by eliminating those antigens responsible for erythema and define a multiantigen mRNA vaccine that blocks tick feeding and transmission of tickborne pathogens while eliciting no local erythema at the bite site.