Date of Award

12-2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program

Biomedical Sciences

Track

Microbiology, Immunology, and Biochemistry

Research Advisor

Maria Gomes-Solecki, DVM

Committee

Robert Belland, PhD Mark Bix, PhD Maureen A. McGargill, PhD Susan E. Senogles, PhD

Keywords

Lyme Disease, Borrelia burgdorferi, Oral Vaccines, Immunology, Leptospirosis, Melioidosis

Abstract

Lyme Disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. If left untreated, it can lead to permanent damage to the nervous and musculoskeletal systems. In some cases, patients that receive the recommended antibiotic therapy develop a debilitating health condition associated with substantial health care costs. Despite current preventive measures, the incidence and the geographic distribution of Lyme Disease continues to increase. Recent estimates from CDC suggest that the true number of cases of Lyme Disease in the US is approximately 300,000 per year. Yet, there is currently no vaccine available for human use, and thus novel strategies to diminish the risk of human exposure to Borrelia burgdorferi are of utmost importance. In an effort to address this need, we developed and tested an array of oral vaccine candidates based on recombinant E. coli that express B. burgdorferi’s OspC type K, OspB, BBK32, and Ixodes scapularis Salp15 and Salp25. Only oral immunization with live E. coli expressing OspC K induced systemic immune responses characterized by high levels of OspC K-specific IgG antibodies in sera as well as IgA antibodies in mucosal secretions, obtained from C3H-HeN mice. Vaccine efficacy studies demonstrated that OspC K-vaccinated mice were not protected from infection when challenge was performed via the natural route of disease transmission using ticks infected with multiple strains of B. burgdorferi, as assessed by the presence of antibodies to B. burgdorferi coupled with positive cultures and f B. burgdorferi is transmitted via ticks harboring also other types of OspCs. Our positive q-PCR results from bladder, heart and ear. Most importantly, we have shown that antibodies specific to OspC type K do not protect mice from infection when the homologous type of B. burgdorferi is transmitted via ticks harboring also other types of OspCs. Our findings are both critical and relevant, and should be considered in future studies involving the design and development of OspC-based vaccines against Lyme Disease.

DOI

10.21007/etd.cghs.2015.0209

Comments

Six month embargo expired June 2016

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