| Autor: |
Holanda RA; Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.; Laboratório de Biologia Parasitária, Universidade CEUMA, Maranhão, Brazil., Muñoz JE; Departamento de Microbiologia, Universidade de São Paulo, São Paulo, Brazil.; Escuela de Medicina y Ciencias de la Salud, Universidad del Rosario, Bogotá, Colombia., Dias LS; Departamento de Microbiologia, Universidade de São Paulo, São Paulo, Brazil., Silva LBR; Departamento de Microbiologia, Universidade de São Paulo, São Paulo, Brazil., Santos JRA; Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.; Laboratório de Microbiologia Ambiental, Universidade CEUMA, Maranhão, Brazil., Pagliari S; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Santa Catarina, Brazil., Vieira ÉLM; Faculdade de Medicina, Universidade Federal de Minas Gerais, Minas Gerais, Brazil., Paixão TA; Departamento de Patologia Geral, Universidade Federal de Minas Gerais, Minas Gerais, Brazil., Taborda CP; Departamento de Microbiologia, Universidade de São Paulo, São Paulo, Brazil., Santos DA; Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil., Bruña-Romero O; Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.; Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina, Santa Catarina, Brazil. |
| Abstrakt: |
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. |
