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Infection and Immunity, December 1998, p. 5763-5770, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Function and Protective Capacity of Treponema
pallidum subsp. pallidum Glycerophosphodiester
Phosphodiesterase
Caroline E.
Cameron,
Christa
Castro,
Sheila A.
Lukehart, and
Wesley C.
Van
Voorhis*
Department of Medicine, University of
Washington, Seattle, Washington
Received 22 June 1998/Returned for modification 18 August
1998/Accepted 11 September 1998
Infectious syphilis, caused by the spirochete bacterium
Treponema pallidum subsp. pallidum, remains a
public health concern worldwide. The immune-response evasion mechanisms
employed by T. pallidum are poorly understood, and
prior attempts to identify immunoprotective antigens for subsequent
vaccine design have been unsuccessful. Previous investigations
conducted in our laboratory identified the T. pallidum
glycerophosphodiester phosphodiesterase as a potential immunoprotective
antigen by using a differential immunologic expression library screen.
In studies reported here, heterologous expression of the T. pallidum glycerophosphodiester phosphodiesterase in
Escherichia coli yielded a full-length, enzymatically active protein. Characterization of the recombinant molecule showed it
to be bifunctional, in that it exhibited specific binding to human
immunoglobulin A (IgA), IgD, and IgG in addition to possessing enzymatic activity. IgG fractionation studies revealed specific binding
of the recombinant enzyme to the Fc fragment of human IgG, a
characteristic that may play a role in enabling the syphilis spirochete
to evade the host immune response. In further investigations, immunization with the recombinant enzyme significantly protected rabbits from subsequent T. pallidum challenge,
altering lesion development at the sites of challenge. In all cases,
animals immunized with the recombinant molecule developed atypical
pale, flat, slightly indurated, and nonulcerative reactions at the
challenge sites that resolved before lesions appeared in the control
animals. Although protection in the immunized rabbits was incomplete,
as demonstrated by the presence of T. pallidum in the
rabbit infectivity test, glycerophosphodiester phosphodiesterase
nevertheless represents a significantly immunoprotective T. pallidum antigen and thus may be useful for inclusion in an
antigen cocktail vaccine for syphilis.
*
Corresponding author. Mailing address: Department of
Medicine, Box 357185, University of Washington, Seattle, WA 98195. Phone: (206) 543-0821. Fax: (206) 685-8681. E-mail:
wesley{at}u.washington.edu.
Infection and Immunity, December 1998, p. 5763-5770, Vol. 66, No. 12
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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