Polyvalent mRNA vaccine targeting outer surface protein C affords multi-strain protection against Lyme disease
There is currently no Lyme disease (LD) vaccine available for use in humans. Outer surface protein C (OspC) of the causative agent, Borrelia burgdorferi, is a promising LD vaccine target. However, the extensive genetic variation of OspC poses a challenge in affording broad protection. Here, we developed a monovalent mRNA vaccine encoding OspC type A and a polyvalent vaccine encoding OspC types A, C, I, K, and N. The monovalent vaccine conferred complete protection against homologous challenge in mice, inducing functional OspC-specific antibodies and CD4⁺ T cell responses. The polyvalent formulation elicited antibodies to all encoded OspC types and protected against strains expressing OspC types A, I, and K, but not C or N. Increasing the dose enhanced protection against the OspC type C strain. This study is the first demonstration of an effective OspC-targeted mRNA vaccine and supports the development of OspC-based vaccines for broad LD prevention.
Authors
- Richard T. Marconi (ORCID: https://orcid.org/0000-0002-6035-7306)
- Jianguo Wu (ORCID: https://orcid.org/0000-0001-5025-5026)
- Levi A. Tamming (ORCID: https://orcid.org/0000-0003-2851-7311)
- Maarten J. Voordouw (ORCID: https://orcid.org/0000-0001-9384-0436)
- Weigang Qiu (ORCID: https://orcid.org/0000-0003-4585-1872)
- Casey Lansdell (ORCID: https://orcid.org/0000-0002-6994-4398)
- Grant Frahm
- Wanyue Zhang
- Marybeth Creskey (ORCID: https://orcid.org/0000-0002-5884-1051)
- Simon Sauvé (ORCID: https://orcid.org/0000-0002-9620-4889)
- Sathya N. Thulasi Raman
- Annabelle Pfeifle
- Heather G. Coatsworth (ORCID: https://orcid.org/0000-0003-3865-394X)
- Caroline Gravel
- Xu Zhang (ORCID: https://orcid.org/0000-0001-8783-8890)
- Xuguang Li (ORCID: https://orcid.org/0000-0003-1155-9128)
- Michael Johnston (ORCID: https://orcid.org/0000-0002-4931-7485)
- Rose Anderson-Duvall
- Lisheng Wang (ORCID: https://orcid.org/0009-0003-6836-6156)
Institutions
- Health Canada (CA)
- University of Ottawa (CA)
- City University of New York (US)
- Public Health Agency of Canada (CA)
- Virginia Commonwealth University (US)
- University of Saskatchewan (CA)
- Hunter College (US)
- Carleton University (CA)
Publication Details
- Journal
- npj Vaccines
- Published
- 2025-12-04
- DOI
- https://doi.org/10.1038/s41541-025-01326-3
- Primary Topic
- Vector-borne infectious diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Government of Canada
- National Institutes of Health
- Health Canada
- National Institute of Allergy and Infectious Diseases