Abstract

The rabbit model of Lyme disease allows for the study of B. burgdorferi in the host adapted state. Rabbits infected with Borrelia burgdorferi (Bb) naturally clear the infection within 5 months and are then immune to challenge by both host adapted Borrelia administered by skin implantation and needle injected in vitro cultivated bacteria. Interestingly, in the rabbit model OspA vaccination does not convey protection against host-adapted borrelia and only minimal protection against needle challenge of in vitro cultivated bacteria. Proteins expressed specifically by host adapted Borrelia (HAB) may contribute to protective immunity in the rabbit. However, studies with outer membrane vesicle preparations (OMV) obtained from in vitro cultivated spirochetes indicate that development of protective immunity is multifactorial since vaccination with OMVs also conveys protection at least against needle challenge. Based on these observations the applicants ask the following questions: 1) what level of protection can be achieved by OMV immunization; 2) what role do OMV immunogens play in protective immunity; 3) and what role do proteins selectively expressed by HAB play in infection derived immunity. And lastly they seek to evaluate the unique properties of HAB and define their role in pathogenesis and immunity. To assess these questions they will: a) isolate HAB from rabbit tissue for use in a variety of analyses described below b) they will determine the kinetics of growth of HAB in the rabbit host c) they will use OMV preparations derived from HAB to determine if they confer protective immunity against challenge with both homologous and heterologous strains. If successful these studies will significantly enhance our understanding of protective immunity in the rabbit, allow for the identification of novel immunogens and contribute to efforts to develop Lyme disease vaccines and diagnostic assays.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
2R01AI037312-06
Application #
2902519
Study Section
Special Emphasis Panel (ZRG1-VACC (01))
Program Officer
Baker, Phillip J
Project Start
1994-09-30
Project End
2004-06-30
Budget Start
1999-07-01
Budget End
2000-06-30
Support Year
6
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Crother, Timothy R; Champion, Cheryl I; Whitelegge, Julian P et al. (2004) Temporal analysis of the antigenic composition of Borrelia burgdorferi during infection in rabbit skin. Infect Immun 72:5063-72
Crother, Timothy R; Champion, Cheryl I; Wu, Xiao-Yang et al. (2003) Antigenic composition of Borrelia burgdorferi during infection of SCID mice. Infect Immun 71:3419-28
Shang, E S; Wu, X Y; Lovett, M A et al. (2001) Homologous and heterologous Borrelia burgdorferi challenge of infection-derived immune rabbits using host-adapted organisms. Infect Immun 69:593-8
Chong-Cerrillo, C; Shang, E S; Blanco, D R et al. (2001) Immunohistochemical analysis of Lyme disease in the skin of naive and infection-immune rabbits following challenge. Infect Immun 69:4094-102
Exner, M M; Wu, X; Blanco, D R et al. (2000) Protection elicited by native outer membrane protein Oms66 (p66) against host-adapted Borrelia burgdorferi: conformational nature of bactericidal epitopes. Infect Immun 68:2647-54
Shang, E S; Champion, C I; Wu, X Y et al. (2000) Comparison of protection in rabbits against host-adapted and cultivated Borrelia burgdorferi following infection-derived immunity or immunization with outer membrane vesicles or outer surface protein A. Infect Immun 68:4189-99
Blanco, D R; Whitelegge, J P; Miller, J N et al. (1999) Demonstration by mass spectrometry that purified native Treponema pallidum rare outer membrane protein 1 (Tromp1) has a cleaved signal peptide. J Bacteriol 181:5094-8
Zhang, H H; Blanco, D R; Exner, M M et al. (1999) Renaturation of recombinant Treponema pallidum rare outer membrane protein 1 into a trimeric, hydrophobic, and porin-active conformation. J Bacteriol 181:7168-75
Blanco, D R; Champion, C I; Lewinski, M A et al. (1999) Immunization with Treponema pallidum outer membrane vesicles induces high-titer complement-dependent treponemicidal activity and aggregation of T. pallidum rare outer membrane proteins (TROMPs). J Immunol 163:2741-6
Shang, E S; Skare, J T; Exner, M M et al. (1998) Isolation and characterization of the outer membrane of Borrelia hermsii. Infect Immun 66:1082-91

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