# Heritable immunization of the white-footed mouse reservoir of Lyme disease

> **NIH NIH R01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $957,529

## Abstract

Project Summary ​ ​ RFA-AI-19-037
The rising incidence of Lyme disease demands new strategies for prevention. Existing methods
such as acaricides, deer reduction, landscaping, and personal protective clothing, are inherently
short-term and must be regularly re-applied, maintained and worn. ​The Mice Against Ticks
project seeks to develop a durable one-time intervention to disrupt the ecological
cycle of Lyme disease transmission for many decades​. The causative agent of Lyme
disease ​B. burgdorferi ​is passed back and forth between ticks and their small animal hosts,
which serve as zoonotic reservoirs of disease. The white-footed mouse ​P. leucopus​ is widely
considered to be the most important reservoir because it is both ubiquitous and extremely
efficient at acquiring and transmitting pathogens via ticks. Our overarching goal for this
proposed project is to heritably immunize white-footed mice against Lyme by encoding
protective ​P​. ​leucopus​ antibodies targeting ​B. burgdorferi ​outer surface protein A (OspA) in the
mouse germline. According to our calculations, combining at least four such antibodies should
prevent evolutionary escape by ​B. burgdorferi ​because too many simultaneous OspA mutations
would be needed. Crucially, even if these mice are less important in some areas than currently
thought, immunization will reduce the number of infected ticks, which in turn will infect fewer
secondary reservoirs, which will infect fewer ticks, reinforcing a negative feedback spiral
anticipated to greatly reduce the local burden of Lyme disease. We have already successfully
isolated anti-OspA antibodies from OspA-immunized ​P. leucopus​, derived putative ​P. leucopus
embryonic stem cells, and shown that the albumin locus appears suitable for antibody secretion
from the liver. We now seek to (1) identify antibodies that bind to at least four different OspA
epitopes, (2) establish a stable embryonic stem cell line and perform germline editing, and (3)
generate heritably resistant mice that express antibodies from a cisgenic cassette linked to a
reciprocal chromosomal translocation, a naturally occurring form of high-threshold gene drive
that would enable the reversible and tightly localized engineering of wild ​P. leucopus
populations. Our open and community-guided approach has met with apparent enthusiasm by
residents of Nantucket and Martha’s Vineyard, indicating that local communities suffering from
tick-borne disease throughout the Northeast and Upper Midwest may wish to immunize their
own wild mouse populations in order to help prevent Lyme disease for many decades.

## Key facts

- **NIH application ID:** 9989482
- **Project number:** 1R01AI152209-01
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Kevin Esvelt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $957,529
- **Award type:** 1
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989482

## Citation

> US National Institutes of Health, RePORTER application 9989482, Heritable immunization of the white-footed mouse reservoir of Lyme disease (1R01AI152209-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9989482. Licensed CC0.

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