mRNA vaccination induces tick resistance and prevents transmission of the Lyme disease agent.

ticks transmit many pathogens that cause human disease, including . Acquired resistance to due to repeated tick exposure has the potential to prevent tick-borne infectious diseases, and salivary proteins have been postulated to contribute to this process. We examined the ability of lipid nanoparticle–containing nucleoside-modified mRNAs encoding 19 salivary proteins (19ISP) to enhance the recognition of a tick bite and diminish engorgement on a host and thereby prevent infection. Guinea pigs were immunized with a 19ISP mRNA vaccine and subsequently challenged with . Animals administered 19ISP developed erythema at the bite site shortly after ticks began to attach, and these ticks fed poorly, marked by early detachment and decreased engorgement weights. 19ISP immunization also impeded transmission in the guinea pigs. The effective induction of local redness early after attachment and the inability of the ticks to take a normal blood meal suggest that 19ISP may be used either alone or in conjunction with traditional pathogen-based vaccines for the prevention of Lyme disease, and potentially other tick-borne infections.