Important note: Information in this article was accurate in January 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, January 11, 1999
Daniel J. DeNoon, Senior Editor
A University of Washington research team reports that a recombinant enzyme derived from the syphilis bacterium - glycerophosphodiester phosphodiesterase or Gpd - is the best single vaccine antigen tested to date.
Vaccination with the antigen didn't protect rabbits against T. pallidum infection. But it did significantly reduce the severity and time-to-clearance of lesions resulting from T. pallidum challenge.
"Although complete protection in the Gpd-immunized animals was not observed ... the degree of protection conferred by immunization with the recombinant Gpd molecule nevertheless is impressive," wrote Caroline E. Cameron and colleagues. "To our knowledge, Gpd represents the first defined antigenic vaccine to demonstrate this level of protection upon T. pallidum challenge."
Cameron et al. reported their findings in the journal Infection and Immunity ("Function and Protective Capacity of Treponema pallidum subsp. pallidum Glycerophosphodiester Phosphodiesterase," Infect Immun, 1998;66(12):5763-70).
Decades of effort have failed to find immunostimulatory T. pallidum antigens suitable for use in a subunit vaccine. In fact, the only vaccines capable of complete protection are whole killed organisms administered in complicated regimens.
Taking a deductive approach, Cameron and colleagues noted that systemic opsonic antibody appears in protected rabbits immediately prior to T. pallidum clearance. They therefore screened a T. pallidum genomic expression library for reactivity with opsonic rabbit serum. This method led to the identification of Gpd as a potential immunoprotective antigen (Stebeck, C.E. et al., FEMS Microbiol Lett, 1997;154:303-10).
Ironically, anti-Gpd antiserum apparently is not opsonic, as it fails to enhance macrophage phagocytosis of T. pallidum. But the antigen's capacity to elicit some degree of protection may be a crucial breakthrough in the syphilis vaccine logjam.
"Further studies will be performed to determine whether alternative methods of Gpd expression, purification, or vaccine delivery, or covaccination with other promising immunoprotective antigens as part of a vaccine cocktail, can achieve complete immunity against T. pallidum challenge," Cameron et al. promised.
This work was supported by grants from the National Institutes of Health and by postdoctoral fellowships from the Natural Sciences and Engineering Research Council of Canada and the Medical Research Council of Canada.
The corresponding author for this study is Wesley C. Van Voorhis, Department of Medicine, Box 357185, University of Washington, Seattle, Washington 98195. Phone: (206) 543-0821. Fax: (206) 685-8681. Email: <wesley@u.washington.edu>.
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