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A double-blinded, placebo-controlled field trial of an OspA-based oral reservoir targeted vaccine against Borrelia burgdorferi
Journal article   Open access   Peer reviewed

A double-blinded, placebo-controlled field trial of an OspA-based oral reservoir targeted vaccine against Borrelia burgdorferi

Amy M Schwartz, Ferney Henao-Ceballos, Kathryn Arnold, Julia Poje, Max Waugh, Greg Joyner, Jose F Azevedo, Tyler Baccam, Eric Kontowicz, Kurayi Mahachi, …
npj vaccines
05/11/2026
DOI: 10.1038/s41541-026-01440-w
PMID: 42115648
url
https://doi.org/10.1038/s41541-026-01440-wView
Published (Version of record) Open Access

Abstract

Lyme disease, caused by Borrelia burgdorferi and transmitted by Ixodes scapularis ticks, remains a significant vector-borne illness in the United States. Small mammal reservoirs, particularly Peromyscus leucopus, play a critical role in B. burgdorferi maintenance. Here, we conducted a five-year, randomized, double-blinded, placebo-controlled field trial deploying an oral OspA-based reservoir-targeted vaccine (RTV) across seven Maryland sites. Bayesian modeling provided estimates of vaccine impact on mouse anti-OspA antibody levels, nymphal tick infection prevalence (NIP), mouse infection rates, and seroconversion to B. burgdorferi in hunting dogs. RTV sites exhibited an estimated 10.5% proportional increase in protective murine anti-OspA antibody levels and a 15.4% reduction in NIP by year five. We also found a lower infection prevalence in mouse blood-fed nymphal ticks (9.8%). RTV sites exhibited modest decreases in mouse infection prevalence, and dog seroconversion rates were similar between groups. Our results indicate that anti-OspA antibody in vaccinated-infected/uninfected P. leucopus reduced B. burgdorferi summertime larval infection prevalence, measured as NIP reductions the following spring. This suggests that OspA-based oral RTV reduces B. burgdorferi transstadial transmission within tick populations. Our findings advance the development of reservoir-targeted solutions for Lyme disease prevention. Further evaluation of impacts on incidental hosts is needed.

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