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P08.04 Pathogenicity of plasmid positive and negative chlamydia trachomatis in a macaque model of ocular and genital tract diseases
  1. DL Patton1,
  2. YTC Sweeney1,
  3. L Kari2,
  4. GL Sturdevant2,
  5. HD Caldwell2
  1. 1University of Washington, Seattle, WA, USA
  2. 2Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA


Introduction Previous studies demonstrated that a Chlamydia trachomatis plasmid negative ocular strain (A/P-) resulted in attenuation of infection and pathology, paired with immune stimulation that produced protective immunity in a monkey ocular model. Expanding upon these findings, we assessed a plasmid negative genital strain (D/P-) in the pigtailed macaque model of chlamydial reproductive tract infection. Infection and pathology were compared to a plasmid positive genital strain  (D/P+).

Methods Groups of six macaques were cervically challenged with C. trachomatis D/P+ or D/P-. All animals were followed for infection, circulating antibody, local immunity, and tissue inflammation. Upon spontaneous clearance of cervical infection, each animal underwent repeated challenges with matched strains to drive upper reproductive tract disease. The same strains were similarly compared in the macaque ocular infection model.

Results Similar rates and duration of chlamydial genital infection were documented in both the P+ and P- challenged macaques. Likewise serum and local antibodies were similar. Tissue inflammation graded by gross observation during laparoscopic procedures and by tissue histology yielded no discernible patterns to disease pathology between P+ and P- strains.

Because A/P+ and A/P- ocular strains in macaques exhibited dramatic differences in infectivity and pathology in the eye, we ocularly challenged animals with D/P+ and D/P-. Unexpectedly, no differences in infectivity or pathology were observed between the D/P+ and D/P- strains; each produced similar infection kinetics with ocular disease characterised by conjunctival hyperemia and follicle formation.

Conclusions Unlike the ocular strain, the plasmid negative genital strain is not attenuated in either genital or ocular macaque  infection models. This suggests that genetic determinants unrelated to the plasmid play a dominant role in the pathogenesis of urogenital strains.

Disclosure of interest statement This research was supported by NIH Contract Numbers HHSN266200700013C and HHSN272201400016C, and by the Office of Research Infrastructure Programs (ORIP) of the National Institutes of Health through Grant Number P51 OD010425 Washington National Primate Research Centre. No pharmaceutical grants were received in the development of this study.

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