A β-mannan trisaccharide conjugate vaccine aids clearance of Candida albicans in immunocompromised 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.
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
Tomasz
T
Lipinski
Xiangyang
X
Wu
Joanna
J
Sadowska
Erin
E
Kreiter
Yutaka
Y
Yasui
Shilton
S
Cheriaparambil
Robert
R
Rennie
David R
DR
Bundle
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D001769:Blood / Q000382:microbiology; D002176:Candida albicans / Q000276:immunology*; D002177:Candidiasis / Q000628:therapy*; D015169:Colony Count, Microbial; D003176:Complement C3 / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005657:Fungal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D016469:Fungemia / Q000517:prevention & control; D016867:Immunocompromised Host; D007074:Immunoglobulin G / Q000097:blood; D008351:Mannans / Q000008:administration & dosage* / Q000276:immunology; D011817:Rabbits; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D016896:Treatment Outcome; D014312:Trisaccharides / Q000008:administration & dosage; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000908:Antibodies, Fungal; D003176:Complement C3; D005657:Fungal Vaccines; D007074:Immunoglobulin G; D008351:Mannans; D013745:Tetanus Toxoid; D014312:Trisaccharides; D018074:Vaccines, Conjugate; C041524:aluminum sulfate