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; Paige Witucki; Suman Kundu; Nisha Nair; Felix Pabon-Rodriguez; Grant Brown; Christine Petersen; Maria Gomes-Solecki; Maryland Field Team

doi:10.64898/2026.04.21.719976

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

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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, …

bioRxiv

Cold Spring Harbor Laboratory

04/22/2026

DOI: 10.64898/2026.04.21.719976

PMID: 42079258

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Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. 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 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 development of reservoir targeted solutions for Lyme disease prevention. Further evaluation of impacts on incidental hosts is needed.

Details

Title: Subtitle: A double-blinded, placebo-controlled field trial of an OspA-based oral reservoir targeted vaccine against Borrelia burgdorferi
Creators: Amy M Schwartz - University of Iowa
Ferney Henao-Ceballos - University of Iowa
Kathryn Arnold - University of Iowa
Julia Poje - University of Iowa
Max Waugh - University of Iowa
Greg Joyner - University of Tennessee Health Science Center
Jose F Azevedo - University of Tennessee Health Science Center
Tyler Baccam - University of Iowa
Eric Kontowicz - University of Iowa
Kurayi Mahachi - University of Iowa
Paige Witucki - University of Iowa
Suman Kundu - University of Tennessee Health Science Center
Nisha Nair - University of Tennessee Health Science Center
Felix Pabon-Rodriguez - Indiana University School of Medicine
Grant Brown - University of Iowa
Christine Petersen
Maria Gomes-Solecki - University of Iowa
Maryland Field Team
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.64898/2026.04.21.719976
PMID: 42079258
ISSN: 2692-8205
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory; United States
Language: English
Date posted: 04/22/2026
Academic Unit: Epidemiology; Emergency Medicine; Biostatistics
Record Identifier: 9985160454102771

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