Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection
AuthorAlves Santos, Julliana Ribeiro
Assuncão Holanda, Rodrigo
Santos Dias, Lucas
Roque Silva, Leandro Buffoni
Alves Santos, Julliana Ribeiro
Alves Paixão, Tatiane
Pelleschi Taborda, Carlos
Assis Santos, Daniel
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.
Epitope ; Gamma Interferon ; Interleukin 1 ; Interleukin 12 ; Interleukin 4 ; Recombinant Vaccine ; Tumor Necrosis Factor ; 43 Kda Protein, Paracoccidioides ; Cytokine ; Epitope ; Fungal Protein ; Fungus Antigen ; Fungus Vaccine ; Glycoprotein ; Recombinant Vaccine ; Virus Like Particle Vaccine ; Animal Cell ; Animal Experiment ; Animal Model ; Animal Tissue ; Cd4+ T Lymphocyte ; Cellular Immunity ; Centrifugation ; Chimera ; Colony Forming Unit ; Controlled Study ; Dna Replication ; Drug Formulation ; Enzyme Linked Immunosorbent Assay ; Hepatitis B ; Histopathology ; Human ; Human Cell ; Immunization ; Immunophenotyping ; Immunoprophylaxis ; Lymphocyte Proliferation ; Magnitude Estimation Method ; Male ; Mortality ; Mouse ; Nonhuman ; Peptide Synthesis ; Plasmid ; Polyacrylamide Gel Electrophoresis ; Protein Expression ; Solid Phase Extraction ; South American Blastomycosis ; Tissue Injury ; Transmission Electron Microscopy ; Vaccine Immunogenicity ; Virus Particle ; Western Blotting ; Animal ; Bagg Albino Mouse ; Cd4+ T Lymphocyte ; Genetics ; Growth, Development And Aging ; Hepatitis B Virus ; Immunological Memory ; Immunology ; Liver ; Lung ; Microbiology ; Paracoccidioides ; Paracoccidioidomycosis ; Secretion (Process) ; Spleen ; Th1 Cell ; Animals ; Antigens, Fungal ; Cd4-Positive T-Lymphocytes ; Cytokines ; Epitopes, T-Lymphocyte ; Fungal Proteins ; Fungal Vaccines ; Glycoproteins ; Hepatitis B Virus ; Immunization ; Immunodominant Epitopes ; Immunogenicity, Vaccine ; Immunologic Memory ; Liver ; Lung ; Mice, Inbred Balb C ; Paracoccidioides ; Paracoccidioidomycosis ; Spleen ; Th1 Cells ; Vaccines, Synthetic ; Vaccines, Virus-Like Particle ;
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