Proteins normally found on the surface of the Lyme disease spirochete, Borrelia burgdorferi, affect the antigenicity, immunological reactivity and host cell interaction of the spirochete. These proteins are the major focus of current efforts to develop safe, effective vaccines to prevent Lyme disease. The overall efficacy of a recombinant vaccine will depend upon the selection of one or more immunoprotective target(s). Genetic variation, particularly the heterogeneity of surface proteins, can alter the antigenicity of the immunoprotective epitopes of the target proteins. Rational development of effective vaccines, therefore, requires determination of the sequence variation of the major outer surface proteins in B. burgdorferi and integration of this knowledge with the tertiary structure of these proteins to help define those regions where changes will influence interaction with antibodies. In order to provide a starting point to elucidate the molecular details of the interactions of the Borrelia surface proteins with the immune system we-. are attempting to use crystallographic techniques to solve the structures of Borrelia's major outer surface proteins alone and in complexes with Fab fragments of protective monoclonal antibodies. Experiments are also described aimed at development of multipeptide chimers to expand the immunoprotective potential of a given vaccine candidate. In particular, we shall -determine the location of protective epitopes within the outer surface proteins and then use these regions to construct multipeptide recombinant hybrids that would extend immunization simultaneously to more than one genospecies and therefore have broad applic ions- in prevention and diagnosis of Lyme disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI037256-04
Application #
2517276
Study Section
Special Emphasis Panel (SRC (75))
Project Start
1994-09-30
Project End
1999-08-31
Budget Start
1997-09-01
Budget End
1999-08-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
State University New York Stony Brook
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Martin, Che L; Martin, Che I; Sukarna, Tika Y et al. (2015) Phylogenomic identification of regulatory sequences in bacteria: an analysis of statistical power and an application to Borrelia burgdorferi sensu lato. MBio 6:
Di, Lia; Pagan, Pedro E; Packer, Daniel et al. (2014) BorreliaBase: a phylogeny-centered browser of Borrelia genomes. BMC Bioinformatics 15:233
Mongodin, Emmanuel F; Casjens, Sherwood R; Bruno, John F et al. (2013) Inter- and intra-specific pan-genomes of Borrelia burgdorferi sensu lato: genome stability and adaptive radiation. BMC Genomics 14:693
Schutzer, Steven E; Fraser-Liggett, Claire M; Qiu, Wei-Gang et al. (2012) Whole-genome sequences of Borrelia bissettii, Borrelia valaisiana, and Borrelia spielmanii. J Bacteriol 194:545-6
Casjens, Sherwood R; Mongodin, Emmanuel F; Qiu, Wei-Gang et al. (2012) Genome stability of Lyme disease spirochetes: comparative genomics of Borrelia burgdorferi plasmids. PLoS One 7:e33280
Casjens, Sherwood R; Mongodin, Emmanuel F; Qiu, Wei-Gang et al. (2011) Whole-genome sequences of two Borrelia afzelii and two Borrelia garinii Lyme disease agent isolates. J Bacteriol 193:6995-6
Casjens, Sherwood R; Fraser-Liggett, Claire M; Mongodin, Emmanuel F et al. (2011) Whole genome sequence of an unusual Borrelia burgdorferi sensu lato isolate. J Bacteriol 193:1489-90
Schutzer, Steven E; Fraser-Liggett, Claire M; Casjens, Sherwood R et al. (2011) Whole-genome sequences of thirteen isolates of Borrelia burgdorferi. J Bacteriol 193:1018-20
Haven, James; Vargas, Levy C; Mongodin, Emmanuel F et al. (2011) Pervasive recombination and sympatric genome diversification driven by frequency-dependent selection in Borrelia burgdorferi, the Lyme disease bacterium. Genetics 189:951-66
Hughes, Jessica L; Nolder, Christi L; Nowalk, Andrew J et al. (2008) Borrelia burgdorferi surface-localized proteins expressed during persistent murine infection are conserved among diverse Borrelia spp. Infect Immun 76:2498-511

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