The most prominent feature of the surface of T. pallidum has been the absence of detectable surface antigens. However, there is evidence that targets of bactericidal antibodies are located in the outer membrane. Mice immunized with T. pallidum outer membrane vesicles have developed killing activity. 30-fold higher than that of immune rabbit serum (IRS). We identified a monoclonal antibody, designated M131, with potent bactericidal activity. M131 and IRS were used to passively immunize rabbits. IRS administration did not result in delays in the appearance of syphilitic lesions compared to controls. M131 administration resulted in a mean 8-day delay in lesion appearance at 17/24 sites. Lesions never developed at the remaining 7/24 sites. These findings are consistent with a greater than 100-fold reduction in the numbers of T. pallidum. This is a greater degree of protection achieved by administration of serum in the rabbit model than has previously been reported. The epitope bound by M131 is an antigen readily detected on the T. pallidum surface by immunoelectron microscopy and by the gel microdroplet method. This is the first instance in which a T. pallidum surface antigen has been demonstrated. The M131 epitope is based upon phosphatidylcholtne (PC) in a membrane form, and requires a threshold concentration of membranous PC for its formation. The M131 epitope is unrelated to the phosphorylcholine epitope found decorating surface proteins of Neisseria, Hemophilus, and Pseudomonas. It constitutes the first reported lipid antigen of T. pallidum. This proposal has three major goals. We will determine the greatest degree of protection that the M131 epitope can convey in the rabbit model of syphilis. We will use monoclonal antibodies with T. pallidum killing activity to identify novel T. pallidum killing targets/surface antigens. We will also explore whether the M131 epitope, and other surface antigens can be found on the surface of the T. palllidum subspecies, including T. pallidum subsp. pallidum street strains, and whether they convey cross-subspecies protection.
