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Updated: Dec 27, 2025
Detecting the Lyme Disease Spirochete, Borrelia Burgdorferi, in Ticks Using Nested PCR
Published on: February 4, 2018
The Factor H-Binding Site of CspZ as a Protective Target against Multistrain, Tick-Transmitted Lyme Disease
Ashley L Marcinkiewicz1, Ilva Lieknina2, Xiuli Yang3
1Division of Infectious Diseases, Wadsworth Center, New York State Department of Health, Albany, New York, USA.
Insights
A modified Borrelia burgdorferi protein, CspZ-YA, shows promise as a Lyme disease vaccine. Unlike the original CspZ protein, CspZ-YA effectively protects mice from infection without triggering harmful immune responses against host factors.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- * *Borrelia burgdorferi sensu lato* causes Lyme disease.
- * The spirochete produces CspZ protein to evade host complement system via binding to factor H (FH).
- * Vaccination with CspZ protein has not proven effective against Lyme disease.
Purpose of the Study:
- * To evaluate the efficacy of a modified CspZ protein (CspZ-YA) lacking FH-binding activity as a Lyme disease vaccine candidate.
- * To compare the immune response and protective efficacy of CspZ-YA vaccination against wild-type CspZ vaccination.
Main Methods:
- * Mice were immunized with either CspZ or CspZ-YA.
- * Vaccinated mice were infected with *Borrelia burgdorferi sensu lato* via tick feeding.
- * Sera from vaccinated mice were analyzed for spirochete elimination activity, FH-binding blocking, and anti-FH antibody production.
Main Results:
- * Immunization with CspZ-YA protected mice against infection by multiple spirochete genotypes.
- * Sera from CspZ-YA-vaccinated mice showed enhanced spirochete elimination and blocked CspZ FH-binding more effectively than sera from CspZ-vaccinated mice.
- * CspZ vaccination, but not CspZ-YA, induced antibodies against host factor H.
Conclusions:
- * CspZ-YA is a promising candidate for a Lyme disease vaccine.
- * The lack of anti-FH antibody production in response to CspZ-YA contributes to its protective efficacy.
- * This study provides mechanistic insights for developing a CspZ-based Lyme disease vaccine.
Abstract:
The spirochete Borrelia burgdorferisensu lato is the causative agent of Lyme disease (LD). The spirochetes produce the CspZ protein that binds to a complement regulator, factor H (FH). Such binding downregulates activation of host complement to facilitate spirochete evasion of complement killing. However, vaccination with CspZ does not protect against LD infection. In this study, we demonstrated that immunization with CspZ-YA, a CspZ mutant protein with no FH-binding activity, protected mice from infection by several spirochete genotypes introduced via tick feeding. We found that the sera from CspZ-YA-vaccinated mice more efficiently eliminated spirochetes and blocked CspZ FH-binding activity than sera from CspZ-immunized mice. We also found that vaccination with CspZ, but not CspZ-YA, triggered the production of anti-FH antibodies, justifying CspZ-YA as an LD vaccine candidate. The mechanistic and efficacy information derived from this study provides insights into the development of a CspZ-based LD vaccine.
