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.