title: Additive effect of P10 immunization and chemotherapy in anergic mice challenged intratracheally with virulent yeasts of Paracoccidioides brasiliensis.
abstract: Paracoccidioidomycosis is a systemic granulomatous disease manifested in the acute/subacute or chronic forms. The anergic cases of the acute/subacute form are most severe, leading to death threatening conditions. Drug treatment is required to control the disease but the response in anergic patients is generally poor. A 15-mer peptide from the major diagnostic antigen gp43, named P10, induces a T-CD4+ helper-1 immune response in mice of different haplotypes and protects against intratracheal challenge with virulent P. brasiliensis. Presently, P10 immunization and chemotherapy were associated in an attempt to improve antifungal treatment in Balb/c mice made anergic by adding dexamethasone to the drinking water. The combined drug/peptide treatment significantly reduced the lung CFUs in infected anergic mice, largely preserved lung alveolar structure and prevented fungal dissemination to liver and spleen. Results recommend that a P10-based vaccine should be associated to chemotherapy for improved treatment of paracoccidioidomycosis aiming especially at anergic cases.
authors.affiliation: Institute of Biomedical Sciences, Department of Microbiology, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Alexandre F
authors.initials: AF
authors.lastname: Marques
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: da Silva
authors.forename: Maria A P
authors.initials: MA
authors.lastname: Juliano
authors.forename: Julian E
authors.initials: JE
authors.lastname: Munhõz
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Travassos
authors.forename: Carlos P
authors.initials: CP
authors.lastname: Taborda
mesh_terms: D000818:Animals; D000908:Antibodies, Fungal / Q000097:blood; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000946:Antigens, Fungal / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D015169:Colony Count, Microbial; D003907:Dexamethasone / Q000008:administration & dosage; D004357:Drug Synergism; D005656:Fungal Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D005657:Fungal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D006023:Glycoproteins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D007114:Immunization; D017964:Itraconazole / Q000008:administration & dosage / Q000627:therapeutic use; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides / Q000276:immunology / Q000472:pathogenicity*; D010229:Paracoccidioidomycosis / Q000188:drug therapy / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D010455:Peptides / Q000008:administration & dosage* / Q000276:immunology; D014132:Trachea / Q000382:microbiology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage / Q000627:therapeutic use; D014774:Virulence
chemical_list: C103180:43 kDa protein, Paracoccidioides; D000908:Antibodies, Fungal; D000935:Antifungal Agents; D000946:Antigens, Fungal; D005656:Fungal Proteins; D005657:Fungal Vaccines; D006023:Glycoproteins; D010455:Peptides; D017964:Itraconazole; D003907:Dexamethasone; D015662:Trimethoprim, Sulfamethoxazole Drug Combination