A novel glyco-conjugate vaccine against fungal pathogens.
To generate a vaccine to protect against a variety of human pathogenic fungi, we conjugated laminarin (Lam), a well-characterized but poorly immunogenic beta-glucan preparation from the brown alga Laminaria digitata, with the diphtheria toxoid CRM197, a carrier protein used in some glyco-conjugate bacterial vaccines. This Lam-CRM conjugate proved to be immunogenic and protective as immunoprophylactic vaccine against both systemic and mucosal (vaginal) infections by Candida albicans. Protection probably was mediated by anti-beta-glucan antibodies as demonstrated by passive transfer of protection to naive mice by the whole immune serum, the immune vaginal fluid, and the affinity-purified anti-beta-glucan IgG fractions, as well as by administration of a beta-glucan-directed IgG2b mAb. Passive protection was prevented by adsorption of antibodies on Candida cells or beta-glucan particles before transfer. Anti-beta-glucan antibodies bound to C. albicans hyphae and inhibited their growth in vitro in the absence of immune-effector cells. Remarkably, Lam-CRM-vaccinated mice also were protected from a lethal challenge with conidia of Aspergillus fumigatus, and their serum also bound to and markedly inhibited the growth of A. fumigatus hyphae. Thus, this novel conjugate vaccine can efficiently immunize and protect against two major fungal pathogens by mechanisms that may include direct antifungal properties of anti-beta-glucan antibodies.
Torosantucci
Antonella
A
Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy.
Bromuro
Carla
C
Chiani
Paola
P
De Bernardis
Flavia
F
Berti
Francesco
F
Galli
Chiara
C
Norelli
Francesco
F
Bellucci
Cinzia
C
Polonelli
Luciano
L
Costantino
Paolo
P
Rappuoli
Rino
R
Cassone
Antonio
A
D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D001228:Aspergillosis / Q000276:immunology / Q000517:prevention & control*; D001232:Aspergillus fumigatus / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002176:Candida albicans / Q000276:immunology* / Q000378:metabolism; D002181:Candidiasis, Vulvovaginal / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D005657:Fungal Vaccines / Q000276:immunology*; D005936:Glucans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008817:Mice, Mutant Strains; D011134:Polysaccharides / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D012698:Serologic Tests; D018074:Vaccines, Conjugate; D047071:beta-Glucans / Q000276:immunology
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D005657:Fungal Vaccines; D005936:Glucans; D011134:Polysaccharides; D018074:Vaccines, Conjugate; D047071:beta-Glucans; C028581:CRM197 (non-toxic variant of diphtheria toxin); C008247:laminaran