The major protein and glycoprotein antigens of Treponema pallidum, Nichols strain, will be identified by polyacrylamide gel electrophoresis, Western blotting and gel immunoreactivity (GIRA) techniques, and immunoprecipitation of antigens with multivalent antisera and monoclonal antibodies. The antigenic structure of the Nichols strain will be compared to that of several nonpathogenic treponemes as well as pathogens including T. pertenue and """"""""street strains"""""""" of T. pallidum. The major antigens of T. pallidum, Nichols strain, will be isolated and partially purified. The immunologic responses of infected rabbits and humans to each of these antigens will be evaluated by serologic testing as well as by lymphocyte transformation, lymphokine release, neutralization, and opsonization assays. Following immunization of rabbits with the isolated antigens, humoral and cellular responses of the artifically immunized animals will be measured by the assays described above. In addition, these immunized animals will be challenged with virulent T. pallidum in order to assess the degree of protection conferred by the individual antigens. It is anticipated that these studies will provide a better understanding of the pathogenesis of syphilis and may lead to the identification of antigens which could serve as the basis for more specific serodiagnostic tests and, ultimately, the development of effective immunization procedures.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI018988-03
Application #
3128406
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1984-03-01
Project End
1987-02-28
Budget Start
1986-03-01
Budget End
1987-02-28
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Cameron, C E; Castro, C; Lukehart, S A et al. (1999) Sequence conservation of glycerophosphodiester phosphodiesterase among Treponema pallidum strains. Infect Immun 67:3168-70
Centurion-Lara, A; Castro, C; Barrett, L et al. (1999) Treponema pallidum major sheath protein homologue Tpr K is a target of opsonic antibody and the protective immune response. J Exp Med 189:647-56
Centurion-Lara, A; Castro, C; Castillo, R et al. (1998) The flanking region sequences of the 15-kDa lipoprotein gene differentiate pathogenic treponemes. J Infect Dis 177:1036-40
Cameron, C E; Castro, C; Lukehart, S A et al. (1998) Function and protective capacity of Treponema pallidum subsp. pallidum glycerophosphodiester phosphodiesterase. Infect Immun 66:5763-70
Centurion-Lara, A; Arroll, T; Castillo, R et al. (1997) Conservation of the 15-kilodalton lipoprotein among Treponema pallidum subspecies and strains and other pathogenic treponemes: genetic and antigenic analyses. Infect Immun 65:1440-4
Centurion-Lara, A; Castro, C; Shaffer, J M et al. (1997) Detection of Treponema pallidum by a sensitive reverse transcriptase PCR. J Clin Microbiol 35:1348-52
Stebeck, C E; Shaffer, J M; Arroll, T W et al. (1997) Identification of the Treponema pallidum subsp. pallidum glycerophosphodiester phosphodiesterase homologue. FEMS Microbiol Lett 154:303-10
Centurion-Lara, A; Castro, C; van Voorhis, W C et al. (1996) Two 16S-23S ribosomal DNA intergenic regions in different Treponema pallidum subspecies contain tRNA genes. FEMS Microbiol Lett 143:235-40
van Voorhis, W C; Barrett, L K; Nasio, J M et al. (1996) Lesions of primary and secondary syphilis contain activated cytolytic T cells. Infect Immun 64:1048-50
Marra, C M; Longstreth Jr, W T; Maxwell, C L et al. (1996) Resolution of serum and cerebrospinal fluid abnormalities after treatment of neurosyphilis. Influence of concomitant human immunodeficiency virus infection. Sex Transm Dis 23:184-9

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