title: The monoclonal antibody against the major diagnostic antigen of Paracoccidioides brasiliensis mediates immune protection in infected BALB/c mice challenged intratracheally with the fungus.
abstract: The protective role of specific antibodies against Paracoccidioides brasiliensis is controversial. In the present study, we analyzed the effects of monoclonal antibodies on the major diagnostic antigen (gp43) using in vitro and in vivo P. brasiliensis infection models. The passive administration of some monoclonal antibodies (MAbs) before and after intratracheal or intravenous infections led to a reduced fungal burden and decreased pulmonary inflammation. The protection mediated by MAb 3E, the most efficient MAb in the reduction of fungal burden, was associated with the enhanced phagocytosis of P. brasiliensis yeast cells by J774.16, MH-S, or primary macrophages. The ingestion of opsonized yeast cells led to an increase in NO production by macrophages. Passive immunization with MAb 3E induced enhanced levels of gamma interferon in the lungs of infected mice. The reactivity of MAb 3E against a panel of gp43-derived peptides suggested that the sequence NHVRIPIGWAV contains the binding epitope. The present work shows that some but not all MAbs against gp43 can reduce the fungal burden and identifies a new peptide candidate for vaccine development.
authors.affiliation: Institute of Biomedical Sciences, Department of Microbiology, University of São Paulo, Ave. Prof. Lineu Prestes, São Paulo, SP 05508-900, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Buissa-Filho
authors.forename: R
authors.initials: R
authors.lastname: Puccia
authors.forename: A F
authors.initials: AF
authors.lastname: Marques
authors.forename: F A
authors.initials: FA
authors.lastname: Pinto
authors.forename: J E
authors.initials: JE
authors.lastname: Muñoz
authors.forename: J D
authors.initials: JD
authors.lastname: Nosanchuk
authors.forename: L R
authors.initials: LR
authors.lastname: Travassos
authors.forename: C P
authors.initials: CP
authors.lastname: Taborda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000946:Antigens, Fungal / Q000737:chemistry / Q000276:immunology*; D002460:Cell Line; D002478:Cells, Cultured; D000939:Epitopes / Q000737:chemistry; D005656:Fungal Proteins / Q000737:chemistry / Q000276:immunology*; D006023:Glycoproteins / Q000737:chemistry / Q000276:immunology*; D007116:Immunization, Passive; D007275:Injections, Intravenous; D016676:Macrophages, Alveolar / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010228:Paracoccidioides / Q000276:immunology / Q000472:pathogenicity*; D010229:Paracoccidioidomycosis / Q000175:diagnosis / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D010587:Phagocytosis; D014132:Trachea / Q000382:microbiology*; D016896:Treatment Outcome
chemical_list: C103180:43 kDa protein, Paracoccidioides; D000911:Antibodies, Monoclonal; D000946:Antigens, Fungal; D000939:Epitopes; D005656:Fungal Proteins; D006023:Glycoproteins