Intranasal vaccine for Lyme disease provides protection against tick transmitted Borrelia burgdorferi beyond one year

Strategies for disease control are necessary to reduce incidence of Lyme Disease (LD) including development of safe vaccines for human use. Parainfluenza virus 5 (PIV5) vector has an excellent safety record in animals and PIV5-vectored vaccines are currently under clinical development. We constructed PIV5-vectored LD vaccine candidates expressing OspA from B. burgdorferi (OspA B31 ) and a chimeric protein containing sequences from B. burgdorferi and B. afzelii (OspA BPBPk ). Immunogenicity and vaccine efficacy were analyzed in C3H-HeN mice after prime-boost intranasal vaccination with live PIV5-OspA B31 or PIV5-OspA BPBPk , subcutaneous (s.c.) vaccination with rOspA B31 +Alum, and the respective controls. Mice vaccinated intranasally with live PIV5-A B31 or PIV5-A BPBPk had higher endpoint titers of serum antibody against OspA B31 at 6- and 12- months post vaccination, compared to mice vaccinated s.c. with rOspA B31 . Neutralization activity of antibody was maintained up to 18-months post-immunization, with the response greater in live PIV5-delivered OspA vaccines, than that induced by s.c. rOspA B31 . Challenge with infected ticks carrying 10-19 strains of B. burgdorferi performed at 4-, 9- or 15-months post-immunization showed increased breakthrough infections in mice vaccinated with s.c. rOspA B31 compared to intranasal PIV5-A B31 or PIV5-A BPBPk at 9- and 15-months, as determined by quantification of serologic antibodies to B. burgdorferi proteins as well as flaB DNA in tissues, and by visualization of motile B. burgdorferi in culture of tissues under dark field microscope. These findings indicate that immunization of mice with PIV5 delivered OspA generates immune responses that produce longer-lasting protection ( > 1 year) against tick-transmitted B. burgdorferi than a parenteral recombinant OspA vaccine.