Journal Article

A β-mannan trisaccharide conjugate vaccine aids clearance of Candida albicans in immunocompromised rabbits

Rennie, Robert, Wu, Xiangyang, Sadowska, Joanna, Lipinski, Tomasz, Bundle, David R., Kreiter, Erin, Yasui, Yutaka, Cheriaparambil, Shilton

2012

Overview

► A synthetic β-(1→2)-linked mannose trisaccharide Candida albicans conjugate vaccine. ► Two injections with alum induce a robust secondary antibody response in rabbits. ► Antibodies recognized the cell wall β-mannan on hyphae and budding cells. ► C. albicans incubated with immune sera bound complement factor C3. ► The vaccine reduces C. albicans fungal burden in leukocytopenic rabbits. A β-(1→2)-linked mannose trisaccharide epitope that is the optimal inhibitor of two protective monoclonal antibodies specific for the Candida albicans cell wall phosphomannan was used to create a synthetic conjugate vaccine. Two injections of the trisaccharide-tetanus toxoid conjugate administered with alum induced a robust secondary antibody response in rabbits with trisaccharide specific IgG ELISA titers in excess of 1:100,000. Fluorescent labeling studies demonstrated these antibodies (i) recognized the cell wall β-mannan of C. albicans on hyphae and budding cells and (ii) C. albicans incubated with immune sera bound complement factor C3. The synthetic conjugate vaccine but not the carrier protein, tetanus toxoid reduced Candida load in vaccinated rabbits subsequently rendered leukocytopenic by injection of cyclophosphamide and then challenged with live C. albicans. These data support the contention that antibody mediated immunity plays a role in combating C. albicans infections and suggests that a surprisingly simple, readily accessible synthetic conjugate vaccine may have therapeutic potential.

• Publisher: Elsevier Ltd
• Subject: Adjuvants, Immunologic - administration & dosage / Allergy and Immunology / alum / Alum Compounds - administration & dosage / Animals / Antibodies, Fungal - blood / Antibody mediated clearance of Candida albicans / antiserum / Blood - microbiology / Candida albicans / Candida albicans - immunology / Candida albicans beta mannan trisaccharide epitope / Candidiasis - therapy / cell walls / Colony Count, Microbial / complement / Complement C3 - immunology / Cyclophosphamide / Disease Models, Animal / Enzyme-Linked Immunosorbent Assay / epitopes / Female / fluorescent labeling / Fungal Vaccines - administration & dosage / Fungal Vaccines - immunology / Fungemia - prevention & control / hyphae / immunity / Immunocompromised Host / Immunocompromised rabbit Candida model / immunoglobulin G / Immunoglobulin G - blood / Mannans - administration & dosage / Mannans - immunology / mannose / monoclonal antibodies / Rabbits / tetanus / Tetanus Toxoid - administration & dosage / Tetanus Toxoid - immunology / Treatment Outcome / Trisaccharide tetanus toxoid conjugate vaccine / Trisaccharides - administration & dosage / vaccines / Vaccines, Conjugate - administration & dosage / Vaccines, Conjugate - immunology