RESUMO
The conventional treatment for fungal diseases usually shows long periods of therapy and the high frequency of relapses and sequels. New strategies of the treatment are necessary. We have shown that the Mycobacterium leprae HSP65 gene can be successfully used as therapy against murine Paracoccidioidomycosis (PCM). Here, we described the methodology of DNAhsp65 immunotherapy in mice infected with the dimorphic fungus Paracoccidioides brasiliensis, one of PCM agent, evaluating cytokines levels, fungal burden, and lung injury. Our results provide a new prospective on the immunotherapy of mycosis.
Assuntos
Antígenos de Bactérias/imunologia , Proteínas de Bactérias/imunologia , Chaperonina 60/imunologia , Vacinas Fúngicas/imunologia , Paracoccidioidomicose/imunologia , Vacinas de DNA/imunologia , Animais , Anticorpos/imunologia , Especificidade de Anticorpos/imunologia , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Chaperonina 60/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Vacinas Fúngicas/genética , Imunoterapia/métodos , Ativação Linfocitária/imunologia , Camundongos , Óxido Nítrico/metabolismo , Paracoccidioidomicose/microbiologia , Paracoccidioidomicose/prevenção & controle , Paracoccidioidomicose/terapia , Plasmídeos/genética , Baço/imunologia , Baço/metabolismo , Baço/patologia , Vacinas de DNA/genéticaRESUMO
Vaccines play an essential role in keeping humans healthy. Innovative approaches to their use include the utilization of plasmid DNA encoding sequences to express foreign antigens. DNAhsp65 from Mycobacterium leprae is suitable for this purpose due to its ability to elicit a powerful immune response. Controlled release systems represent a promising approach to delivering vaccines. In this work, we used liposomes or PLGA systems to deliver DNAhsp65 to treat the pulmonary fungal infection Paracoccidioidomycosis. Both formulations modulated a protective immune response and reduced the pulmonary fungal burden even in the groups receiving less than four times the amount of the DNAhps65 entrapped within the nanoparticles. Although both systems had the same effective therapeutic results, the advantage of the liposome formulation was that it was administered intranasally, which may be more easily accepted by patients. These systems are a great alternative to be considered as adjuvant vaccine therapy for systemic mycosis.
Assuntos
Biotecnologia/métodos , Vacinas Fúngicas/administração & dosagem , Técnicas de Transferência de Genes , Nanotecnologia/métodos , Paracoccidioidomicose/imunologia , Paracoccidioidomicose/prevenção & controle , Vacinas de DNA/administração & dosagem , Animais , Proteínas de Bactérias/metabolismo , Proliferação de Células , Chaperonina 60/metabolismo , Citocinas/metabolismo , Vacinas Fúngicas/imunologia , Imunidade Humoral/imunologia , Imunoglobulina G/sangue , Ácido Láctico/química , Lipossomos/química , Pulmão/imunologia , Pulmão/microbiologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium leprae/metabolismo , Óxido Nítrico/metabolismo , Paracoccidioides/fisiologia , Paracoccidioidomicose/sangue , Paracoccidioidomicose/microbiologia , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Baço/metabolismo , Vacinas de DNA/imunologiaRESUMO
The conventional treatment for paracoccidioidomycosis, the most prevalent mycosis in Latin America, involves long periods of therapy resulting in sequels and high frequency of relapses. The search for new alternatives of treatment is necessary. Previously, we have demonstrated that the hsp65 gene from Mycobacterium leprae shows prophylactic effects against murine paracoccidioidomycosis. Here, we tested the DNAhsp65 immunotherapy in BALB/c mice infected with Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis. We observed an increase of Th1 cytokines accompanied by a reduction in fungal burden and pulmonary injury. These results provide new prospects for immunotherapy of paracoccidioidomycosis and other mycoses.
Assuntos
Proteínas de Bactérias/imunologia , Chaperonina 60/imunologia , Imunoterapia/métodos , Mycobacterium leprae/imunologia , Paracoccidioidomicose/prevenção & controle , Vacinas de DNA/imunologia , Animais , Proteínas de Bactérias/genética , Chaperonina 60/genética , Citocinas/metabolismo , Pulmão/microbiologia , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mycobacterium leprae/genética , Paracoccidioides/imunologia , Vacinas de DNA/administração & dosagemRESUMO
Heat-shock proteins are molecules with extensive data showing their potential as immunomodulators of different types of diseases. The gene of HSP65 from Mycobacterium leprae has shown prophylactic and immunotherapeutic effects against a broad arrays of experimental models including tuberculosis, leishmaniasis, arthritis and diabetes. With this in mind, we tested the DNAhsp65 vaccine using an experimental model of Paraccocidiodomycosis, an important endemic mycosis in Latin America. The intramuscular immunization with DNAhsp65 induced, in BALB/c mice, an increase of Th1-levels cytokines and a reduction of fungal burdens resulted in a marked reduction of collagen and lung remodeling. DNAhsp65 may be an attractive candidate for prevention, therapy and as an adjuvant for mycosis treatment.