The Factor H-Binding Site of CspZ as a Protective Target against Multistrain, Tick-Transmitted Lyme Disease
Year: 2020
Type: article
Abstract: 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.
Source: Infection and Immunity
DOI: 10.1128/iai.00956-19
Institutions: New York State Department of Health, Wadsworth Center, Latvian Biomedical Research and Study Centre, Virginia–Maryland College of Veterinary Medicine, University of Maryland, College Park, State University of New York, University at Albany, State University of New York, Baylor College of Medicine, Texas Children's Hospital, Baylor University, University Hospital Frankfurt
Language: English
Subfield: Parasitology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: BBA57-Mediated Borrelial Persistence, Genesis of Inflammation and Immunity, Collaborative Research: Tradeoffs between specialist and generalist strategies for host immune evasion in a vector-borne bacterium, Multiple B. burgdorferi Factors Collaborate to Evade Complement-Mediated Defenses, G3147923281, Identification of the mechanism of protection against a B. burgdorferi protein CspZ for the prevention of Lyme disease, Borrelia gene products critical for natural infection cycle, G8122428412
OpenAlex ID: W3009720467