| dc.description.abstract | Lyme disease (LD), one of the most common tick-borne diseases in the Northern Hemisphere, is caused by Borreliella (Borrelia) burgdorferi (B. burgdorferi). The lack of vaccine, increases in LD cases, and wide distribution of Ixodes ticks necessitate the development of an LD vaccine for humans. Identification of protection-associated (PA) epitopes that could lead to the development of a second-generation vaccine against LD is, therefore, needed. Despite the presence of numerous antigenic proteins on the borrelial surface, VlsE is the only variable protein that undergoes rigorous antigenic variation Although VlsE-mediated shielding of a surface antigen was recently demonstrated, it is unlikely that VlsE covers an entire surface of B. burgdorferi. Thus, it is hypothesized that only dominant epitopes are masked by VlsE, whereas subdominant epitopes remain exposed. Moreover, some exposed epitopes may induce protection when made dominant.
The first study presented herein focused on the identification of surface epitopes that could
provide protection despite VlsE. For that, immunocompetent mice were repeatedly immunized with VlsE-deficient B. burgdorferi and then challenged with wild-type (VlsEexpressing) B. burgdorferi. As a result, 50% of mice became protected due to the repeated exposure of surface epitopes in the absence of VlsE. Subsequently, antibody repertoires identified by random phage display libraries were defined and compared between protected and non-protected mice, which allowed us to pinpoint putative PA epitopes. The second study has examined a protective antibody response in the New Zealand White (NZW) rabbit model. In contrast to mice, NZW rabbits were previously shown to mount a protective antibody response against wild-type B. burgdorferi. A series of passive immunization experiments demonstrated that anti-B. burgdorferi rabbit antibodies provided 100% protection in mice against VlsE-expressing wild type despite the fully functional VlsE system. In addition to protecting against homologous and heterologous challenges, anti-B. burgdorferi rabbit antibodies significantly reduced LD-induced arthritis in actively B. burgdorferi-infected mice. Lastly, the third study has analyzed of the metabiota of Ixodes ricinus, the tick species which is critical in maintaining the enzootic cycle of LD in Europe. The results demonstrated extensive sex-specific and regional-specific variations in the bacterial flora of adult ticks. | |
