Abstract
The concept that fungal vaccines could be useful is no longer merely an illusion. There is a need for either preventive or therapeutic vaccines to curb the rising incidence of fungal infections. With the advent of AIDS and the use of increasingly potent immunosuppressive therapies to combat autoimmune diseases, malignancies, and transplant rejection, the incidence of opportunistic fungal infection has increased. To combat such conditions, an appropriate fungal vaccine needs to be developed apart from antifungal therapy. Prior to the development of any fungal vaccine, one should know the mechanism of immune response elicited by a fungal infection, i.e., both humoral and cell-mediated. In addition, there are dormant states of infection. Because a high proportion of the fungal diseases are thought to involve reactivation of dormant foci, therapeutic immunization becomes a compelling approach to eliminate dormant organisms or to heal active infection, especially in life-threatening disease. In animal models of fungal infection, protective responses have been elicited with vaccines composed of whole organisms, soluble cell-free fractions, purified proteins, glucans, and nucleic acids. Methods to boost the immune response to vaccination include the use of adjuvants and antigen-loaded dendritic cells (DCs). The recognition that antibodies are effective against fungal pathogens has spawned interest in developing vaccines that elicit antibody-mediated protection. Recently, a novel polysaccharide-protein conjugate vaccine that uses the algal antigen laminarin was shown to elicit antibodies to beta-glucan in fungal cell walls, and to mediate protection against both experimental candidiasis and aspergillosis. Conventional methodologies of vaccination are giving way to newer approaches, of which DNA vaccination represents one of the most exciting, not only for fungal diseases but also for all diseases mediated by pathogenic microbes. The primary method at present is to use plasmid-encoded DNA that does not replicate and is delivered by intramuscular injection producing Th1 response, thus clearing the pathogenic fungi. DNA vaccination holds promise in the field of mycology. One of the major controversies and challenges surrounding fungal vaccination is the case of the immunocompromised host. The challenge will be to enhance the effect of a vaccine when the immune system is dysfunctional. One approach would be to link the vaccine with attempts to restore the integrity of the immune system, i.e., the delivery of a vaccine in combination with cytokine or cytokines that are known to enhance the immune system. Another approach would be to link the administration of the vaccine with infusion of immunocompetent T cells or B cells to promote the immunogenicity of the vaccine. Therefore, newer methods are necessary to identify who is at highest risk, in order to determine who would benefit the most from vaccination or a combination of vaccination and immunorestorative therapy.