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Live Attenuated Borrelia burgdorferi Targeted Mutants in an Infectious Strain Background Protect Mice from Challenge
Beth L Hahn1, Lavinia J Padmore1, Laura C Ristow2
1Department of Medicine, Division of Infectious Diseases, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
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. The increasing incidence and geographic spread of Lyme disease are renewing interest in the vaccination of at-risk populations. We took the approach of vaccinating mice with two targeted mutant strains of B. burgdorferi that, unlike the parental strain, are avirulent in mice. Mice vaccinated with both strains were protected against a challenge with the parental strain and a heterologous B. burgdorferi strain by either needle inoculation or tick bite. In ticks, the homologous strain was eliminated but the heterologous strain was not, suggesting that the vaccines generated a response to antigens that are produced by the bacteria both early in mammalian infection and in the tick. Partial protection against B. garinii infection was also conferred. Protection was antibody mediated, and reactivity to a variety of proteins was observed. These experiments suggest that live attenuated B. burgdorferi strains may be informative regarding the identification of protective antigens produced by the bacteria and recognized by the mouse immune system in vivo Further work may illuminate new candidates that are effective and safe for the development of Lyme disease vaccines.
Insights
Researchers developed live attenuated Borrelia burgdorferi strains as a potential Lyme disease vaccine. Vaccinated mice showed protection against challenge, suggesting a promising new avenue for Lyme disease prevention.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Lyme disease, caused by Borrelia burgdorferi and related species, presents a growing public health concern due to increasing incidence and geographic spread.
- Untreated Lyme disease can lead to chronic morbidity, persisting even after antibiotic treatment.
- Renewed interest in vaccination strategies for at-risk populations is driven by the limitations of current treatments and disease prevalence.
Purpose of the Study:
- To evaluate the efficacy of live attenuated Borrelia burgdorferi strains as a vaccine candidate against Lyme disease.
- To identify protective antigens and understand the immune response generated by these attenuated strains.
Main Methods:
- Vaccination of mice with two targeted, avirulent mutant strains of B. burgdorferi.
- Challenge of vaccinated mice with virulent parental and heterologous B. burgdorferi strains via needle inoculation and tick bite.
- Assessment of protection, bacterial elimination in ticks, and antibody-mediated immune responses.
Main Results:
- Mice vaccinated with both attenuated strains demonstrated significant protection against challenge with homologous and heterologous B. burgdorferi strains.
- The homologous vaccine strain was eliminated in ticks, while the heterologous strain persisted, indicating antigen recognition during different infection stages.
- Partial protection was observed against Borrelia garinii infection, and protection was confirmed to be antibody-mediated.
Conclusions:
- Live attenuated B. burgdorferi strains show potential as a vaccine platform for Lyme disease.
- These attenuated strains can help identify protective antigens recognized by the host immune system in vivo.
- Further research into these attenuated strains may lead to the development of safe and effective Lyme disease vaccines.
