Quantitative Assessment of Protection in Experimental Syphilis

• Published in: Infection and Immunity 2005-09, Vol.73 (9), p.5923-5927
• Main Authors: Champion, Cheryl I, Blanco, David R, Lovett, Michael A
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Bacterial diseases; Bacterial diseases of the genital system; Biological and medical sciences; Chemokines, CC; Disease Models, Animal; Fundamental and applied biological sciences. Psychology; Gene Dosage; Human bacterial diseases; Immunization, Passive; Infectious diseases; Medical sciences; Microbial Immunity and Vaccines; Microbiology; Polymerase Chain Reaction; Rabbits; Syphilis - immunology; Syphilis - prevention & control; Treponema pallidum; Treponema pallidum - genetics; Treponema pallidum - immunology; Viral Proteins
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.73.9.5923-5927.2005

Protection in experimental rabbit syphilis has been previously assessed by lesion development following intradermal challenge with Treponema pallidum. We have recently reported that passive immunization using monoclonal antibody M131 conveys partial protection as evidenced by significant lesion delays following intradermal challenge (D. R. Blanco et al., Infect. Immun. 73:3083-3095, 2005). To determine whether such delays in time to lesion appearance corresponded to decreases in the numbers of spirochetes, we used real-time PCR to quantitate T. pallidum genomic DNA copy numbers in lesion biopsies taken throughout the course of lesion development. Three groups of animals were given one prechallenge passive immunization with immune rabbit serum (IRS), M131, or control monoclonal antibody (CMAb) and then challenged with treponemal admixtures of IRS or monoclonal antibody in normal rabbit serum (NRS). As compared to the CMAb NRS controls, delays in the mean time to lesion appearance of 5.8 days for IRS and 8.8 days for M131 were observed. At the earliest time point (10 days postchallenge), real-time PCR showed a mean T. pallidum DNA copy number per [micro]g of rabbit DNA in the CMAb NRS group of 7.65 x 10³ copies, while no T. pallidum DNA could be detected in the M131 group. At approximately the mean time to lesion appearance in the IRS and M131 groups (17 and 20 days, respectively), the numbers of T. pallidum DNA copies were still 5- and 30-fold less, respectively, than those in the control group at these times. By 30 days postchallenge, the T. pallidum DNA copy numbers were similar in all three groups. These findings indicate that the delays in appearance of syphilitic lesions conferred by IRS and M131 corresponded to a marked decrease in treponemal numbers during the course of lesion development.