title: Vaccine progress.
abstract: Despite the recent development of new anti-mould agents, there remains a significant incidence of invasive aspergillosis in the most immunocompromised hosts and the response to these agents is still dismal. There is a need for a different approach: prevention by vaccination. We have demonstrated that a hyphal sonicate of Aspergillus fumigatus was capable of conferring protection against subsequent invasive pulmonary aspergillosis in corticosteroid immunosuppressed mice. Subcutaneous vaccination was superior to nasal vaccination. Mice exposed intranasally to viable conidia were noted to respond serologically to a 19 kDa protein. This protein was identified as the allergen Asp f 3 by mass spectrometry. Vaccination with recombinant Asp f 3 was protective. Truncated forms of Asp f 3 that lacked either one of the two known IgE binding sites were cloned and also demonstrated protection against aspergillosis. Although all of these recombinant proteins required an adjuvant (TiterMax) for efficacy, a particulate preparation of rAsp f 3 was also found to be protective without requiring adjuvant. At least two T-cell epitopes (11-mer and 13-mer) have been identified in Asp f 3. There are homologues of Asp f 3 in other Aspergillus species as well as in other moulds (Coccidioides posadasii, Penicillium citrinum) and yeasts (Candida albicans, C. boidinii, Saccharomyces cerevisiae). Asp f 3, truncated non-allergenic versions of Asp f 3, and T-cells epitopes of Asp f 3 are potential candidates for vaccines potentially capable of protecting immunocompromised hosts against invasive aspergillosis.
authors.affiliation: Division of Infectious Diseases, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010-3000, USA. jito@coh.org
authors.forename: James I
authors.initials: JI
authors.lastname: Ito
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Lyons
authors.forename: Diana
authors.initials: D
authors.lastname: Diaz-Arevalo
authors.forename: Teresa B
authors.initials: TB
authors.lastname: Hong
authors.forename: Markus
authors.initials: M
authors.lastname: Kalkum
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000485:Allergens / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant; D001228:Aspergillosis / Q000276:immunology / Q000517:prevention & control*; D001232:Aspergillus fumigatus / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D005657:Fungal Vaccines / Q000276:immunology*; D016867:Immunocompromised Host; D051379:Mice; D016019:Survival Analysis; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D052179:Antigens, Plant; C115315:Asp f 3 allergen; D018984:Epitopes, T-Lymphocyte; D005657:Fungal Vaccines; D014614:Vaccines, Synthetic