Chlamydia trachomatis is the major cause of preventable blindness in the world. In areas where trachoma is prevalent, virtually every child becomes exposed and may develop the disease. C. trachomatis is the cause of the most common sexually-transmitted disease (STD) in the U.S. as well as other countries and is a major cause of tubal infertility in women which may go unnoticed in many individuals. Both diseases may be treated with antibiotics but may be either logistically difficult as in the treatment of trachoma, or as in chlamydial STD, they may not be administered at all because the patient is unaware of the presence of the disease. The only truly effective control of both diseases would be prophylaxis with a vaccine. Patients with chlamydial genital tract infections respond with antibody to a variety of chlamydial proteins, in particular, the major outer membrane protein (MOMP) and a 60-62K membrane protein. The incidence of the response to MOMP is variable while most patients respond to the 60-62K protein. To determine which antigens are the best candidates for a vaccine, an animal model will be used. Guinea pigs can be infected in the eye and genital tract with the chamydial agent of guinea pig inclusion conjunctivitis (GPIC), a natural parasite of the guinea pig, which produces diseases analogous to the human infections. Guinea pigs also develop antibodies to MOMP and 61K just as humans. Female guinea pigs will be infected either in the genital tract or eye with GPIC and the antibody response in serum and secretions determined by immunoblot analysis. Cell-mediated immunity (CMI) to whole GPIC, MOMP, and 61K will also be measured by blast transformation. Animals will be challenged at varying times, according to the responses to MOMP and 61K to determine whether either is associated with protection. Animals will also be immunized with whole GPIC, MOMP, and 61K to determine if protective immunity can be induced. Various regimens will be used to stimulate preferentially the mucosal-associated lymphoid system. Immune animals will also be teated with anti-thymocyte serum to determine whether CMI is required for immunity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI023044-02
Application #
3134903
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1986-04-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Mallet, Dann G; Heymer, Kelly-Jean; Rank, Roger G et al. (2009) Chlamydial infection and spatial ascension of the female genital tract: a novel hybrid cellular automata and continuum mathematical model. FEMS Immunol Med Microbiol 57:173-82
Nagarajan, U M; O'Connell, C; Rank, R G (2004) Molecular characterization of guinea - pig (Cavia porcellus) CD8alpha and CD8beta cDNA. Tissue Antigens 63:184-9
Rank, Roger G; Bowlin, Anne K; Reed, Ronald L et al. (2003) Characterization of chlamydial genital infection resulting from sexual transmission from male to female guinea pigs and determination of infectious dose. Infect Immun 71:6148-54
Rank, R G; Bowlin, A K; Kelly, K A (2000) Characterization of lymphocyte response in the female genital tract during ascending Chlamydial genital infection in the guinea pig model. Infect Immun 68:5293-8
Darville, T; Andrews Jr, C W; Rank, R G (2000) Does inhibition of tumor necrosis factor alpha affect chlamydial genital tract infection in mice and guinea pigs? Infect Immun 68:5299-305
Wyrick, P B; Knight, S T; Paul, T R et al. (1999) Persistent chlamydial envelope antigens in antibiotic-exposed infected cells trigger neutrophil chemotaxis. J Infect Dis 179:954-66
Patterson, T L; Rank, R G (1996) Immunity to reinfection and immunization of male guinea pigs against urethral infection with the agent of guinea pig inclusion conjunctivitis. Sex Transm Dis 23:145-50
Rank, R G; Dascher, C; Bowlin, A K et al. (1995) Systemic immunization with Hsp60 alters the development of chlamydial ocular disease. Invest Ophthalmol Vis Sci 36:1344-51
Darville, T; Laffoon, K K; Kishen, L R et al. (1995) Tumor necrosis factor alpha activity in genital tract secretions of guinea pigs infected with chlamydiae. Infect Immun 63:4675-81
Rank, R G; Sanders, M M; Patton, D L (1995) Increased incidence of oviduct pathology in the guinea pig after repeat vaginal inoculation with the chlamydial agent of guinea pig inclusion conjunctivitis. Sex Transm Dis 22:48-54

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