Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection

Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay. The highly virulent Pb18 yeast strain was used to challenge our vaccine candidates. Fungal challenge evoked robust P10-specific memory CD4+T cells secreting protective Th-1 cytokines in most groups of immunized mice. Furthermore, the highest level of fungal burden control was achieved when rAdPbT was inoculated in a homologous prime-boost regimen, with 10-fold less CFU recovering than in non-vaccinated mice. Systemic Pb18 spreading was only prevented when rAdPbT was previously inoculated. In summary, we present here VLP/P10 formulations as vaccine candidates against PCM, some of which have demonstrated for the first time their ability to prevent progression of this pernicious fungal disease, which represents a significant social burden in developing countries. © 2017 Holanda et al.

• Fecha de publicación: 2017
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/18682
• Acceso en línea: https://doi.org/10.1371/journal.pntd.0005927; http://repository.urosario.edu.co/handle/10336/18682
• Palabra clave: Epítopo; Partícula similar a un virus; Interferón gamma; Hongos; Sintético; Linfocito T; Balb endogámico C; Paracoccidioides; Desarrollo y Envejecimiento; Vacuna; Interleucina 1; interleucina 12; interleucina 4; Vacuna recombinante; Factor de necrosis tumoral; Proteína de 43 Kda; Citocina; Epítopo; Proteína fúngica; Antígeno de hongos; Vacuna contra hongos; Glicoproteína; Vacuna recombinante; Vacuna contra partículas similares a virus; Célula animal; Experimento con animales; Modelo animal; Tejido animal; Linfocito T Cd4+; Inmunidad celular; Centrifugación; Quimera; Unidad de formación de Colonia; Estudio controlado; Replicación de ADN; Formulación de Medicamentos; Ensayo inmunoabsorbente ligado a enzimas; Hepatitis B; Histopatología; Humano; Célula humana; Inmunización; Inmunofenotipado; Inmunoprofilaxis; Proliferación de linfocitos; Método de estimación de la magnitud; Mortalidad; Síntesis de péptidos; Plásmido; Electroforesis en gel de poliacrilamida; Expresión de proteínas; Extracción de fase sólida; Blastomicosis sudamericana; Lesión de tejido; Microscopio de transmisión por electrones; Inmunogenicidad de la vacuna; Partícula de virus; Transferencia occidental; Ratón albino bagg; Genética; Crecimiento; Hepatitis B Virus; Memoria Inmunológica; Inmunología; Microbiología; Paracoccidioides; Paracoccidioidomicosis; Secreción (Proceso); Célula Th1; Article; Th1 Cell; Secretion (Process); Paracoccidioidomycosis; Microbiology; Liver; Immunology; Immunological Memory; Growth; Genetics; Western Blotting; Bagg Albino Mouse; Virus Particle; Vaccine Immunogenicity; Transmission Electron Microscopy; Tissue Injury; South American Blastomycosis; Solid Phase Extraction; Protein Expression; Polyacrylamide Gel Electrophoresis; Plasmid; Peptide Synthesis; Mortality; Magnitude Estimation Method; Lymphocyte Proliferation; Immunoprophylaxis; Immunophenotyping; Immunization; Human Cell; Human; Histopathology; Enzyme Linked Immunosorbent Assay; Drug Formulation; Dna Replication; Controlled Study; Colony Forming Unit; Chimera; Centrifugation; Cellular Immunity; Cd4+ T Lymphocyte; Animal Tissue; Animal Model; Animal Experiment; Animal Cell; Virus Like Particle Vaccine; Recombinant Vaccine; Glycoprotein; Fungus Vaccine; Fungus Antigen; Fungal Protein; Epitope; Cytokine; 43 Kda Protein; Tumor Necrosis Factor; Recombinant Vaccine; Interleukin 4; Interleukin 12; Interleukin 1; Vaccine; Development And Aging; Paracoccidioides; Inbred Balb C; T-Lymphocyte; Synthetic; Fungal; Gamma Interferon; Virus-Like Particle; Epitope; Glucoproteinas; Paracoccidioidomycosis; Micosis
• License: Abierto (Texto Completo)