Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection
| Autor: | Rodrigo Assuncao Holanda, Tatiane A. Paixão, Leandro Buffoni Roque da Silva, Sthefany Pagliari, Carlos Pelleschi Taborda, Lucas Dos Santos Dias, Julliana Ribeiro Alves Santos, Daniel Assis Santos, Julián E. Muñoz, Érica Leandro Marciano Vieira, Oscar Bruna-Romero |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Protein Expression
Ratón albino bagg Vacuna contra partículas similares a virus Colony Forming Unit Pathology and Laboratory Medicine Interleukin 1 Biochemistry Paracoccidioides Interleukin 4 Animal Cells Desarrollo y Envejecimiento Microscopio de transmisión por electrones Magnitude Estimation Method Lung Immune Response Lesión de tejido Célula humana Vaccines Synthetic Recombinant Vaccines Drug Formulation Vacuna Immunogenicity Solid Phase Extraction Formulación de Medicamentos Virus Particle Experimento con animales Secretion (Process) Método de estimación de la magnitud Cellular Immunity Electroforesis en gel de poliacrilamida Fungal Partícula de virus Viral Pathogens Vacuna recombinante Hepatitis B Virus 030106 microbiology Inmunología Factor de necrosis tumoral Microbiology Article Glucoproteinas 03 medical and health sciences Antigen Expresión de proteínas Genetics Glycoproteins Inmunoprofilaxis Fungal vaccine Human Cell Synthetic Public Health Environmental and Occupational Health Biology and Life Sciences Proteins lcsh:RA1-1270 Animal Experiment Célula Th1 030104 developmental biology Virus Like Particle Vaccine T-Lymphocyte Interferón gamma Tejido animal Proliferación de linfocitos Fungal Vaccines Paracoccidioidomycosis Proteína de 43 Kda Cd4+ T Lymphocyte CD4-Positive T-Lymphocytes Adenoviruses interleucina 12 Physiology Epitopes T-Lymphocyte Growth Plasmid Quimera White Blood Cells Immunogenicity Vaccine Plásmido Development And Aging Medicine and Health Sciences Fungus Antigen Vaccines Immune System Proteins T Cells lcsh:Public aspects of medicine Modelo animal Fungal Diseases interleucina 4 Inbred Balb C Animal Cell Infectious Diseases Th1 Cell Liver Inmunización Extracción de fase sólida Hepatitis B virus Western Blotting Infectious Disease Control Immunophenotyping Fungal Proteins Partícula similar a un virus medicine Animals Antigens Memoria Inmunológica Gamma Interferon Chimera South American Blastomycosis Th1 Cells biology.organism_classification Transferencia occidental Histopatología Blastomicosis sudamericana Transmission Electron Microscopy DNA viruses Linfocito T Inmunidad celular Vaccine Spleen Síntesis de péptidos Microbiología 43 Kda Protein Epitope Hongos Immunoprophylaxis ANTÍGENOS DE FUNGOS Linfocito T Cd4+ Proteína fúngica Fungal protein Vaccine Immunogenicity Inmunofenotipado Vacuna contra hongos Medical Microbiology Interleucina 1 Cytokines Cellular Types Human Antigens Fungal Balb endogámico C lcsh:RC955-962 Immune Cells Immunology Immunological Memory Crecimiento Sintético Epítopo Unidad de formación de Colonia Animal Tissue Secreción (Proceso) Humano Microbial Pathogens Paracoccidioides brasiliensis Fungus Vaccine Blood Cells Tissue Injury Glicoproteína Organisms Citocina medicine.disease Virology Recombinant Vaccine Yeast Infections Inmunogenicidad de la vacuna Centrifugación Animal Model Glycoprotein Replicación de ADN Tumor Necrosis Factor Immunologic Memory 0301 basic medicine Fungal Protein Antígeno de hongos Centrifugation Polyacrylamide Gel Electrophoresis Interleukin 12 Immune Physiology Enzyme Linked Immunosorbent Assay Bagg Albino Mouse Mice Inbred BALB C Micosis Hepatitis B Célula animal Recombinant Proteins Dna Replication Viruses Paracoccidioidomicosis Pathogens Research Article lcsh:Arctic medicine. Tropical medicine Histopathology Biology Lymphocyte Proliferation Vaccines Virus-Like Particle Controlled Study Mortality Peptide Synthesis Cytokine Ensayo inmunoabsorbente ligado a enzimas Immunodominant Epitopes Cell Biology Estudio controlado Genética Virus-Like Particle Mortalidad Immunization |
| Zdroj: | Munoz, J.F., Gallo, J.E., Misas, E., Priest, M., Imamovic, A., Young, S., Genome update of the dimorphic human pathogenic fungi causing paracoccidioidomycosis (2014) Plos Neglect Trop D, 8, p. e3348 Repositorio EdocUR-U. Rosario Universidad del Rosario instacron:Universidad del Rosario Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, Vol 11, Iss 9, p e0005927 (2017) |
| Popis: | 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. Author summary Human paracoccidioidomycosis (PCM) represents a serious public health issue due to its disabling sequelae in working-age people and mortality rates (8th among chronic infectious parasitic diseases in endemic countries and first among mycoses in Brazil). Although antifungal drugs have been widely used and provide clinical improvement for patients, the long duration of treatments (commonly from 6 to 12 months) has contributed to non-compliance and worsening of the disease in many cases. Induction of protective immune responses (either prophylactic or immune-therapeutic) remains the most cost-effective approach against most infectious agents. Members of our group have previously reported the protective properties of P10, a peptide contained in Paracoccidioides brasiliensis gp43 antigen, against PCM. However, the magnitude of the CD4+ T-cell responses elicited lacked the capacity of completely protecting experimental animals. We demonstrate here that immunogenic virus-like particles (VLP) carrying multiple copies of P10 peptide substantially improve P10-related cellular immunity in mice. This was particularly true when an adenoviral immunization vector expressed the chimeric VLP. Moreover, VLP/P10 formulations were capable of controlling the host fungal burden and prevented fungal systemic dissemination. The efficacy of diverse VLP/P10 formulations in murine PCM showed at least one promising candidate vaccine against human PCM. |
| Databáze: | OpenAIRE |
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