NPJ vaccinesDec 4, 2025

mRNA vaccine targeting an outer surface protein provides protection against multiple Lyme disease strains

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

OspC mRNA vaccines protected mice against some Borrelia strains, but polyvalent strain coverage was incomplete.

Evidence

Preclinical mouse vaccine-challenge study tested monovalent OspC type A and polyvalent OspC types A, C, I, K, and N mRNA vaccines against multiple Borrelia burgdorferi strains.

Caveat

The polyvalent vaccine protected against OspC types A, I, and K but not C or N at the tested formulation, and all efficacy evidence was in mice.

Simplified

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.