Evaluation of EcoCRM, virus-like particles, and mRNA as vaccine platforms against Borrelia burgdorferi.

Lyme disease (LD) is the most prevalent vector-borne disease in the United States, impacting ∼476,000 individuals annually with increasing incidence. Prevention relies on personal protective measures such as insecticides and tick checks, underscoring the need for new preventatives such as vaccines. In this work, the importance of vaccine platform in LD vaccine development efforts was evaluated using non-lipidated OspA as model antigen. Recombinant OspA conjugated to CRM197 (EcoCRM OspA), a virus-like particle vaccine utilizing SpyTag and SpyCatcher (OspA-SpyVLP), and an mRNA-based vaccine construct (OspA mRNA) were evaluated and compared in C3H mice using the needle injection challenge model. To determine immunogenicity, anti-OspA and anti-B. burgdorferi antibodies were quantified via ELISA and further assessed by measuring IgG subclass, antibody avidity, and presence of antibody secreting cells. All vaccine formulations were immunogenic and led to the release of similar levels of antigen-specific IgG in serum during the duration of the experiment. However, there were significant differences around two week post-boost in the presence of antibody secreting cells, ratio of IgG1/IgG2 subclasses, and antibody avidity between platforms. Protection was measured using PCR and darkfield microscopy to determine organ positivity post-challenge. Vaccination with recombinant non-lipidated OspA and OspA-SpyVLP significantly reduced the number of positive organs compared to the PBS challenged control group. Lastly, in vitro borreliacidal activity was quantified via darkfield microscopy and the highest borreliacidal activity was observed using OspA-SpyVLP sera, with titers 16-fold higher than recombinant OspA. Altogether, these data indicated that selection of vaccine platform/formulation influenced the immunogenicity and efficacy of OspA-based LD vaccines and should be considered during development.