Homologous and Heterologous Immunization with a PIV5-Based Modified OspA Vaccine Confers Equivalent Protection Against Tick-Transmitted Borrelia burgdorferi

Vaccines targeting outer surface protein A (OspA) of Borrelia burgdorferi protect against Lyme disease by eliciting antibodies that neutralize spirochetes in the Ixodes scapularis tick midgut during engorgement before transmission occurs. We evaluated whether different delivery vehicles and administration routes of a modified OspA construct (OspA BPBPk ) differed in protective efficacy. Four groups of nine C3H-HeN mice were immunized with OspA BPBPk delivered intranasally by live parainfluenza virus 5 (PIV5-A BPBPk ) or by subcutaneous administration of recombinant protein adjuvanted by alum (rOspA BPBPk ) using three prime-boost regimens in comparison with a non-vaccinated control: homologous intranasal PIV5-A BPBPk (IN/IN), homologous subcutaneous rOspA BPBPk (SC/SC), and heterologous intranasal PIV5-A BPBPk prime/subcutaneous rOspA BPBPk boost (IN/SC). Mice were challenged approximately three months after the boost with nymphal ticks infected with 19 strains of B. burgdorferi . All OspA BPBPk -containing vaccines elicited high antigen-specific IgG antibody titers (mean ∼10 5 ) in serum (4 Log 10 higher than control), reduced B. burgdorferi loads in engorged nymphal ticks by 1.7-2 Log 10 , neutralized B. burgdorferi motility in multi-strain cultures, and prevented dissemination of live B. burgdorferi to tissues after tick challenge. While one mouse (1/9, 11%) in the heterologous IN/SC vaccinated group had increased flaB DNA burdens in tissues and some seroreactivity to B. burgdorferi pepVF, culture of spirochetes from heart and bladder showed no evidence of active infection. Although homologous immunization produced the most consistent results, different delivery vehicles and routes of immunization with OspA BPBPk vaccines did not affect overall efficacy based on culture of live B. burgdorferi from tissues.