RESUMO
The Tc24 calcium binding protein from the flagellar pocket of Trypanosoma cruzi is under evaluation as a candidate vaccine antigen against Chagas disease. Previously, a DNA vaccine encoding Tc24 was shown to be an effective vaccine (both as a preventive and therapeutic intervention) in mice and dogs, as evidenced by reductions in T. cruzi parasitemia and cardiac amastigotes, as well as reduced cardiac inflammation and increased host survival. Here we developed a suitable platform for the large scale production of recombinant Tc24 (rTc24) and show that when rTc24 is combined with a monophosphoryl-lipid A (MPLA) adjuvant, the formulated vaccine induces a Th1-biased immune response in mice, comprised of elevated IgG2a antibody levels and interferon-gamma levels from splenocytes, compared to controls. These immune responses also resulted in statistically significant decreased T. cruzi parasitemia and cardiac amastigotes, as well as increased survival following T. cruzi challenge infections, compared to controls. Partial protective efficacy was shown regardless of whether the antigen was expressed in Escherichia coli or in yeast (Pichia pastoris). While mouse vaccinations will require further modifications in order to optimize protective efficacy, such studies provide a basis for further evaluations of vaccines comprised of rTc24, together with alternative adjuvants and additional recombinant antigens.
Assuntos
Antígenos de Protozoários/imunologia , Doença de Chagas/prevenção & controle , Vacinas Protozoárias/imunologia , Trypanosoma cruzi/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/genética , Doença de Chagas/imunologia , Clonagem Molecular , Modelos Animais de Doenças , Escherichia coli/genética , Feminino , Expressão Gênica , Interferon gama/metabolismo , Leucócitos Mononucleares/imunologia , Lipídeo A/administração & dosagem , Camundongos Endogâmicos BALB C , Carga Parasitária , Parasitemia/prevenção & controle , Pichia/genética , Vacinas Protozoárias/administração & dosagem , Vacinas Protozoárias/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Baço/imunologia , Análise de Sobrevida , Células Th1/imunologia , Trypanosoma cruzi/genética , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologiaRESUMO
Fungus from the Aspergillus genus mainly affects lung tissue, occurring when the integrity of the host immunesystem is compromised. The human body uses immunocompetence conditions from mechanical and enzymatic defenses and the action of the innate immune system cells and also uses adaptive responses to control infection. Neutrophils, macrophages, and dendritic cells are critical as antifungal effector cells possess surface receptors that recognize fungal structures and trigger specific responses. TLRs and Dectin-1 the most studied for this interaction. TLRs are responsible for the production and release of cytokines and Dectin-1 is essential in the phagocytosis of theparticle recognition and production of ROS. The best-studied cytokines and its crucial role in the response toAspergillus spp. are TNF-á, IFN-ã, and IL-12. In this work, we reviewed the main mechanisms related to molecularreceptors on phagocytic cells involved in the recognition of Aspergillus spp. Understanding the immune response insituations of immunocompetence and its comparison in immunodeficient organisms could provide alternatives tocontrol invasive aspergillosis.
