# Identification of protective Lyme disease antigens using live attenuated vaccines

> **NIH NIH R01** · MEDICAL COLLEGE OF WISCONSIN · 2020 · $378,200

## Abstract

Borrelia burgdorferi, B. garinii and B. afzelii are all agents of Lyme disease in different geographic locations. If
left untreated, Lyme disease can cause significant and long-term morbidity, which may continue after
appropriate antibiotic therapy has been administered and live bacteria are no longer detectable. There was a
Lyme disease vaccine available for human use from 1998 to 2002, but that vaccine is no longer available. The
vaccine targeted an abundant B. burgdorferi surface lipoprotein, OspA, which is produced by the bacteria
primarily while they reside in the tick and in laboratory culture. This vaccine protected against infection when
bloodstream anti-OspA titer was sufficiently high, but was comprised of only a single OspA variant. Ultimately,
this vaccine afforded ~80% effective protection in the large phase three trial and in subsequent post-market
monitoring, likely at least in part due to the diversity of OspA sequences that was later revealed by genome
and ospA allele sequencing. There was also concern regarding the safety of this vaccine among some groups,
as reactivity to OspA was associated with Lyme arthritis, particularly the treatment-refractory arthritis, although
no increase in arthritis was seen in humans who received the vaccine compared to control groups. The
increasing incidence and geographic spread of Lyme disease, however, is renewing interest in vaccination of
at-risk populations, and is fueled by recent analyses of several data sets that indicate that the Lyme disease
case numbers in the USA may actually be up to ten times higher than the number of cases reported to the
CDC. We took the novel approach of vaccinating mice with two targeted mutant strains of B. burgdorferi that
are avirulent in mice. Mice vaccinated with both strains were protected against challenge by the parental strain
and a heterologous B. burgdorferi strain by either needle inoculation or tick bite. Sera from vaccinated mice
were also protective (conferred “passive immunity”). In ticks, the homologous strain was eliminated but the
heterologous strain was not, suggesting that the vaccines generated a response against antigens that are
produced by the bacteria both early in mammalian infection and in the tick. Partial protection was also
conferred against B. garinii infection. Our hypothesis is that the live attenuated vaccine strains provide
unique tools to identify novel protective antigens. To further characterize the protective response raised
against the live attenuated vaccines, we propose to 1) Identify antigens that are recognized by the sera of
vaccinated mice; 2) Produce and test recombinant versions of these antigens as subunit vaccines; and 3)
Analyze the immune response in immunized mice and evaluate association with susceptibility to arthritis upon
challenge with infectious B. burgdorferi. These experiments will test the novel hypothesis that live attenuated B.
burgdorferi strains can be informative regarding identification of prot...

## Key facts

- **NIH application ID:** 9917694
- **Project number:** 5R01AI121217-05
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Jenifer L Coburn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $378,200
- **Award type:** 5
- **Project period:** 2016-05-19 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9917694

## Citation

> US National Institutes of Health, RePORTER application 9917694, Identification of protective Lyme disease antigens using live attenuated vaccines (5R01AI121217-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9917694. Licensed CC0.

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