A Lyme disease mRNA vaccine targeting Borrelia burgdorferi OspA induces strong immune responses and prevents transmission in mice

Lyme borreliosis (LB), caused by <i>Borrelia burgdorferi</i> sensu lato, is one of the most common tick-borne diseases in the northern hemisphere. Given its increasing global incidence, LB remains a major public health concern and the development of an effective vaccine is recognized as a key component of the overall disease prevention strategy. Here, we present results obtained with newly developed lipid nanoparticle-encapsulated mRNA vaccine candidates encoding the outer surface protein A (OspA) of <i>B. burgdorferi</i> sensu stricto (Bbss) serotype 1 (mRNA-OspA) with or without a secretion signal (SS) or a transmembrane domain. We evaluated the immunogenicity and protective efficacy of the mRNA-OspA vaccine candidates in a tick-fed mouse challenge model compared with an adjuvanted OspA protein subunit vaccine and the licensed canine vaccine Recombitek Lyme. At the doses tested, the mRNA-OspA vaccines induced significantly higher OspA-specific immunoglobulin G titers than the protein-based vaccines, as well as functional antibodies measured by serum bactericidal assay against Bbss strain B31. Complete protection against transmission was observed in the group immunized with the mRNA-OspA without SS. Overall, these data demonstrate that an mRNA-OspA vaccine can be effective against LB infection and could be used in the future for the prevention of Lyme disease.