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Homologous and Heterologous Immunization with a PIV5-Based Modified OspA Vaccine Confers Equivalent Protection Against Tick-Transmitted Borrelia burgdorferi
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Homologous and Heterologous Immunization with a PIV5-Based Modified OspA Vaccine Confers Equivalent Protection Against Tick-Transmitted Borrelia burgdorferi
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Journal Article
Homologous and Heterologous Immunization with a PIV5-Based Modified OspA Vaccine Confers Equivalent Protection Against Tick-Transmitted Borrelia burgdorferi
2026
Overview
Vaccines targeting outer surface protein A (OspA) of
protect against Lyme disease by inducing antibodies in the host that neutralize spirochetes in the
tick midgut during engorgement before transmission occurs. We evaluated whether heterologous vaccination enhances protection compared to homologous delivery of the immunogen. C3H-HeN mice were immunized with a parainfluenza virus 5 vector (PIV5) containing a modified OspA protein (OspA
) using three prime-boost immunization regimens: homologous PIV5 intranasal/intranasal (IN/IN), homologous rOspA
(protein) subcutaneous/subcutaneous (SC/SC), or heterologous intranasal PIV5-A
/subcutaneous rOspA
(IN/SC). Immunized mice were then challenged with nymphal
ticks infected with 19 strains of
three months post-prime vaccination. Three weeks after the last day of tick challenge, blood and tissues were collected from euthanized mice. All OspA-containing regimens elicited strong systemic IgG antibody responses that exceeded established protective thresholds. Vaccination markedly reduced
loads in engorged nymphal ticks. Homologous IN/IN and SC/SC regimens produced the lowest geometric mean
burdens in nymphs (2.6 × 10
and 1.8 × 10
copies, respectively), corresponding to ~1.8-2.0 log
reductions relative to controls; the heterologous IN/SC regimen produced a more modest reduction (~1.7 log
; p = 0.0071 vs IN/IN, p = 0.0003 vs SC/SC). Across all vaccinated groups, no systemic infection with
was observed as evidenced by absence of motile spirochetes in cultures from tissues, although one mouse (1/9, 11%) in the heterologous IN/SC regimen, had evidence of increased pepVF seroconversion and low-level
DNA in culture. Thus, homologous regimens yielded more consistent protective immunity with absent of signs of
dissemination, suggesting that high systemic anti-OspA
IgG antibody titers, rather than alternate immunization routes, were associated with the most consistent protection outcomes. PIV5-A
is a promising vaccine candidate for development of next-generation homologous or heterologous human Lyme disease vaccines.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory Preprints
