We have shown mangabey monkeys (Cecocebus atys atys) to be a model for the study of experimental leprosy. Rhesus (Macaca mulatta) and African green (Cercopithecus aethiops) monkeys show promise of also being susceptible to leprosy. The goals of this proposal are: 1) to continue to study clinically, immunologically and histopathologically untreated and treated mangabeys, rhesus and African green monkeys to further define the course of leprosy; 2) to inoculate additional rhesus and green monkeys to define their susceptibility to experimental leprosy; 3) to study the effects of immunomodulators (thymopoietin, interleukin 2, gamma-interferon, BCG + killed Mycobacterium leprae and possibly transfer factor); 4) to define the relationship of lepromin skin testing to the susceptibility to and course of leprosy in monkeys; 5) to further characterize the mechanism of immune suppression that we have observed in mangabeys with leprosy; 6) to determine if mangabeys can be protected by vaccination with M. leprae antigens against challenge with live M. leprae; and 7) to maintain the established YRPRC mangabey breeding colony to provide animals for leprosy research. Animals will be monitored longitudinally, as we have been doing, before and after vaccination or inoculation or treatment. We will completely characterize animals prior to and at intervals after vaccination and after M. leprae inoculation, and during therapy. Studies will include: serum chemistries and hemograms; physical, clinical and neurological exams; nerve conduction velocities; bacteriologic, histopathologic and immunohistologic examinations of biopsies. Immunologic parameters to be studied are: in vitro mitogen and antigen (e.g., lepromin) responses of lymphocytes (L); in vitro L immunoglobulin (Ig) production; B- and T-L numbers and subpopulations; suppressor/helper T-L activity; natural killer (NK) cell cytotoxicity and antibody-dependent cellular cytotoxicity (ADCC); blood mononuclear cell cyclic-AMP, phosphodiesterase and adenyl cyclase levels; lepromin skin test responses; serum levels of Ig's, C3, C4, immune complexes, prostaglandins, sialic acid, rheumatoid factor, and anti-M. leprae antibody. These studies will further define the susceptibility of monkeys to leprosy; further illuminate the course of leprosy in monkeys; show whether immunotherapy can alter the course of leprosy; and determine whether vaccination may offer protection against experimental leprosy transmission in monkeys.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R22)
Project #
2R22AI019302-04
Application #
3444620
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1982-09-01
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Tulane University
Department
Type
Schools of Medicine
DUNS #
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Gormus, B J; Baskin, G B; Xu, K et al. (2002) Anti-leprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: lepromin skin test results. Lepr Rev 73:254-61
Gormus, B J; Baskin, G B; Xu, K et al. (2000) Antileprosy protective vaccination of rhesus monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations. Int J Lepr Other Mycobact Dis 68:27-39
Gormus, B J; Baskin, G B; Xu, K et al. (2000) Antileprosy protective vaccination of sooty mangabey monkeys with BCG or BCG plus heat-killed Mycobacterium leprae: immunologic observations. Int J Lepr Other Mycobact Dis 68:434-43
Gormus, B J; Xu, K; Cho, S N et al. (1995) Experimental leprosy in monkeys. II. Longitudinal serological observations in sooty mangabey monkeys. Lepr Rev 66:105-25
Gormus, B J; Xu, K; Baskin, G B et al. (1995) Experimental leprosy in monkeys. I. Sooty mangabey monkeys: transmission, susceptibility, clinical and pathological findings. Lepr Rev 66:96-104
Cho, S N; Gormus, B J; Xu, K et al. (1993) Serologic responses to nerve antigens in sooty mangabey monkeys with experimental leprosy. Int J Lepr Other Mycobact Dis 61:236-44
Meyers, W M; Gormus, B J; Walsh, G P et al. (1991) Naturally acquired and experimental leprosy in nonhuman primates. Am J Trop Med Hyg 44:24-7
Gormus, B J; Xu, K Y; Alford, P L et al. (1991) A serologic study of naturally acquired leprosy in chimpanzees. Int J Lepr Other Mycobact Dis 59:450-7
Baskin, G B; Gormus, B J; Martin, L N et al. (1990) Pathology of dual Mycobacterium leprae and simian immunodeficiency virus infection in rhesus monkeys. Int J Lepr Other Mycobact Dis 58:358-64
Gormus, B J; Xu, K; Meyers, W M et al. (1990) Antibodies to lipoarabinomannan antigen in sooty mangabey monkeys experimentally inoculated with Mycobacterium leprae. Int J Lepr Other Mycobact Dis 58:65-72

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