# Polyvalent mRNA vaccine targeting outer surface protein C affords multi-strain protection against Lyme disease

## TL;DR

A new mRNA vaccine targeting a key protein in Lyme disease bacteria offers protection against multiple strains, with potential for broader use.

## Contribution

The first effective OspC-targeted mRNA vaccine is developed, showing multi-strain protection in mice.

## Key findings

- A monovalent mRNA vaccine encoding OspC type A fully protected mice from homologous challenge.
- A polyvalent vaccine induced antibodies against multiple OspC types and protected against some strains.
- Higher doses improved protection against OspC type C, suggesting dose-dependent efficacy.

## Abstract

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.