David R. Bundle1'*, M. Nitz1'2, Xiangyang Wu1, and Joanna M. Sadowska1
department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2, Canada 2Current address: Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada
The cell wall phosphomannan of C. albicans is a promising target for the induction of immunity by development of a conjugate vaccine. It contains a unique antigen, a (31,2-mannan that affords active protection to mice following immunization and subsequent challenge with live organisms. Disaccharide and trisaccharide fragments of the (31,2-mannan antigen optimally inhibit two murine monoclonal antibodies that confer protection in a mouse model of candidiasis implying that epitopes of this size might constitute viable vaccine components. Short oligosaccharides conjugated to suitable immunogenic proteins have been synthesized by two distinct approaches one of which is well suited to multigram synthesis. Tetanus toxoid was chosen as a carrier protein for its ability to induce a vigorous hapten specific IgG response and for compatibility with human vaccine applications. Preliminary data show that rabbits immunized three times with a trisaccharide glycoconjugate produce sera with ELISA titers of 1:500,000 for the Candida albicans cell wall mannan. These rabbit antibodies also bind the antigen when it is present on the fungal cell wall. Only slightly lower antibody responses to the trisaccharide epitope were observed when 2 injections of these tetanus toxoid conjugates was performed with alum, an adjuvant acceptable for use in humans.
© 2008 American Chemical Society
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