Beta-glucan-CRM197 conjugates as candidates antifungal vaccines.
A laminarin-diphtheria toxoid (CRM197) conjugate vaccine conferred protection against fungal infections in mice. We have now generated novel beta-glucan-CRM197 vaccines, with either natural (Curd-CRM197) or synthetic linear (15mer-CRM197), or beta-(1,6)-branched (17mer-CRM197) beta-(1,3)-oligosaccharides, formulated with the human-acceptable adjuvant MF59. Curd-CRM197 and 15mer-CRM197 conjugates, which induced high titers of anti-beta-(1,3)-glucan IgG, but no antibodies against beta-(1,6)-glucan, conferred protection to mice lethally challenged with C. albicans. In contrast, the 17mer-CRM197 conjugate, which induced anti-beta-(1,6)-glucan antibodies in addition to the anti-beta-(1,3)-glucan IgG, was non-protective. These data provide some insights on beta-glucan epitope(s) mediating antifungal protection and open the way to develop a synthetic oligosaccharide vaccine against fungal diseases.
Bromuro
Carla
C
Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy.
Romano
Maria
M
Chiani
Paola
P
Berti
Francesco
F
Tontini
Marta
M
Proietti
Daniela
D
Mori
Elena
E
Torosantucci
Antonella
A
Costantino
Paolo
P
Rappuoli
Rino
R
Cassone
Antonio
A
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D001426:Bacterial Proteins / Q000494:pharmacology*; D005260:Female; D005657:Fungal Vaccines / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D009181:Mycoses / Q000276:immunology / Q000517:prevention & control; D016019:Survival Analysis; D018074:Vaccines, Conjugate / Q000276:immunology; D047071:beta-Glucans / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000908:Antibodies, Fungal; D001426:Bacterial Proteins; D005657:Fungal Vaccines; D007074:Immunoglobulin G; D018074:Vaccines, Conjugate; D047071:beta-Glucans; C028581:CRM197 (non-toxic variant of diphtheria toxin)