Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

Vaccines against opportunistic fungal infections
Antonio Cassone
Department of Infectious, Parasitic and Immuno-mediated Diseases, Istituto Superiore di
Sanità, Rome, Italy.
The rising threat represented by opportunistic fungal infections, the scarcity/high
cost of effective antifungal treatments in the setting of the immunocompromised
host, the advances in the knowledge of fungal pathogenicity and immune responses
are the main driving factors to recent studies aimed at generating active and passive
vaccination tools against human pathogenic fungi. Two vaccines, one specifically
designed to fight chronic recurrent mucosal candidiasis and another one for more
general anti-Candida prevention/therapy, are in clinical trials in Europe and US.
A third vaccine, made up by an algal -glucan (laminarin) conjugated with a protein
component (Lam-CRM vaccine) has been formulated to enter clinical investigation.
This vaccine has been shown to protect against experimental infections by the three
major opportunistic fungi such as Candida albicans, Aspergillus fumigatus and
Cryptococcus neoformans and has been therefore designated as pan-fungal or
“universal” vaccine. Protection appears to be largely if not exclusively mediated by
anti- -glucan antibodies with restricted specificity to 1-3 linked epitope and
capable to inhibit growth and virulence-associated fungal factors. Protective anti-
1-3 glucan monoclonal murine and human-chimeric antibodies have also been
generated thus opening perspectives for passive vaccination in
immunocompromized subjects.
Our research demonstrates the possibility of conveying into a single immunological
tool the potential to protect against multiple fungal infections. The above approach
could be theoretically extended to non-fungal infections by selecting the
appropriate molecular pattern shared by a given microbial group (e.g. peptidoglycan
for Gram-positive bacteria). Noteworthy, the molecular patterns are those highly
conserved pathogen-associated molecules which foster innate immunity through
their binding to the pattern-recognition structures and intracellular signalling, hence
shaping adaptive immune responses. Single-component, molecular pattern-based
vaccines would merge the broad target range typical of innate immunity with the
highly focussed specificity of the adaptive immunity.
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