Previous attempts to produce immunity in syphilis in experimental animals did not provide satisfactory results. The most direct method to determine the mechanism of immunity would be to confer it on normal recipients by transferring antibodies or lymphoid cells from immune animals. Such experimental approach requires inbred animals. Rabbit is the most susceptible laboratory animal for experimental syphilis, but it is far from being the ideal model. Inbred rabbit is not readily available and the responses to T. pallidum infection involve a great deal of non-specificity. Guinea pig, although comparatively less susceptible to infection, responds more restrictively (possible more specific) producing only treponemal IgG antibodies (no IgG or cardiolipin antibodies) and the T cells respond to T. pallidum antigen but not to T. phagedenis Reiter. Guinea pig may provide information not extractable from rabbit. We are proposing to use inbred strain 2 guinea pigs to examine: a) The susceptibility to infection with various wild strains of T. pallidum. If no differences are found the presently established Nichols strain to which they are susceptible up to 100% when used in appropriate concentration will be used for all experiments. b) The time at which the immune resistance is established, and to determine by transfer experiments whether it is controlled by humoral or cellular mechanisms. c) The specificity of the treponemal antibodies produced in guinea pig and compare it with those produced in rabbits. The guinea pig model, in addition to the information on the mechanisms of immunity, may also provide a tool for evaluation of treponemal antigens produced by DNA hybridization or potential vaccines for syphilis; the necessary background information for future studies of the genetic factors controlling immunity and for studying natural resistance to T. pallidum.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI021833-01
Application #
3132216
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1985-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
New York State Department of Health
Department
Type
DUNS #
002436061
City
Menands
State
NY
Country
United States
Zip Code
12204
Wicher, K; Wicher, V; Abbruscato, F et al. (2000) Treponema pallidum subsp. pertenue displays pathogenic properties different from those of T. pallidum subsp. pallidum. Infect Immun 68:3219-25
Wicher, K; Horowitz, H W; Wicher, V (1999) Laboratory methods of diagnosis of syphilis for the beginning of the third millennium. Microbes Infect 1:1035-49
Wicher, K; Baughn, R E; Abbruscato, F et al. (1999) Vertical transmission of Treponema pallidum to various litters and generations of guinea pigs. J Infect Dis 179:1206-12
Wicher, V; Wicher, K; Abbruscato, F et al. (1999) The time-dependent clearance of virulent Treponema pallidum in susceptible and resistant strains of guinea pigs is significantly different. Clin Immunol 91:77-83
Wicher, V; Scarozza, A M; Ramsingh, A I et al. (1998) Cytokine gene expression in skin of susceptible guinea-pig infected with Treponema pallidum. Immunology 95:242-7
Wicher, K; Abbruscato, F; Wicher, V et al. (1998) Identification of persistent infection in experimental syphilis by PCR. Infect Immun 66:2509-13
Scarozza, A M; Ramsingh, A I; Wicher, V et al. (1998) Spontaneous cytokine gene expression in normal guinea pig blood and tissues. Cytokine 10:851-9
Dilwith, R; Wicher, K (1997) CD5+ and CD5- B1-like lymphocytes in healthy guinea pig. Clin Immunol Immunopathol 85:143-50
Wicher, V; Zhao, J; Dilwith, R et al. (1997) Immune abnormalities in guinea pigs with asymptomatic congenital syphilis. Pediatr Res 42:794-8
Wicher, K; Abbruscato, F; Wicher, V et al. (1996) Target organs of infection in guinea pigs with acquired congenital syphilis. Infect Immun 64:3174-9

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