The Journal of Experimental Medicine
Cytokines Montreal 2008
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Published 6 September 2005. doi:10.1084/jem.20050749
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 202, Number 5, 597-606
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ARTICLE

 A novel glyco-conjugate vaccine against fungal pathogens

Antonella Torosantucci1, Carla Bromuro1, Paola Chiani1, Flavia De Bernardis1, Francesco Berti2, Chiara Galli2, Francesco Norelli2, Cinzia Bellucci2, Luciano Polonelli3, Paolo Costantino2, Rino Rappuoli2, and Antonio Cassone1

1 Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, 00186 Rome, Italy
2 Chiron Vaccines, 53100 Siena, Italy
3 Microbiology Section, Department of Pathology and Laboratory Medicine, University of Parma, 43100 Parma, Italy

CORRESPONDENCE Antonio Cassone: cassone{at}iss.it

To generate a vaccine to protect against a variety of human pathogenic fungi, we conjugated laminarin (Lam), a well-characterized but poorly immunogenic ß-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-ß-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-ß-glucan IgG fractions, as well as by administration of a ß-glucan–directed IgG2b mAb. Passive protection was prevented by adsorption of antibodies on Candida cells or ß-glucan particles before transfer. Anti-ß-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-ß-glucan antibodies.

Abbreviations used: CT, cholera toxin; GG, glucan ghosts; Lam, laminarin; NMR, nuclear magnetic resonance; ppm, parts per million; Zym, zymoliase.


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