Rabies virus-vectored Lyme disease vaccine provides long-term protection against tick-transmitted Borrelia burgdorferi.

Lyme disease (LD) cases have doubled globally. LD is a tick-borne illness caused by the Borrelia burgdorferi sensu lato (Bb). If untreated, Bb can disseminate to distal organs, causing carditis, arthritis, and meningitis. Currently, no FDA-approved human LD vaccine exists on the market. This study used two approaches to incorporate OspA into the rabies virus (RABV) vaccine vector. We used the RABV-glycoprotein tail (RVG tail) and the Hendra virus (HeV) glycoprotein tail (HVG tail) to incorporate OspA, creating BNSP333-OspA-RVG and BNSP333-OspA-HVG, respectively. Both vaccines produced type-1 biased anti-OspA antibodies, but only BNSP333-OspA-HVG induced neutralizing antibodies and protected against Bb infection. Furthermore, BNSP333-OspA-HVG was combined with an established LD vaccine, BNSP333-BBI39-dRVG, to study a multivalent LD vaccine. The single and multivalent vaccines produced robust type-1 biased humoral responses and induced protection against Bb after short-term and long-term tick challenge experiments. These findings contributed to the development of future LD vaccines.