RESUMO
This image represents a physician unilaterally completing a do-not-resuscitate order for an unrepresented patient.
RESUMO
Chagas disease, caused by Trypanosoma cruzi, results in an acute febrile illness that progresses to chronic chagasic cardiomyopathy in 30% of patients. Current treatments have significant side effects and poor efficacy during the chronic phase; therefore, there is an urgent need for new treatment modalities. A robust TH1-mediated immune response correlates with favorable clinical outcomes. A therapeutic vaccine administered to infected individuals could bolster the immune response, thereby slowing or stopping the progression of chagasic cardiomyopathy. Prior work in mice has identified an efficacious T. cruzi DNA vaccine encoding Tc24. To elicit a similar protective cell-mediated immune response to a Tc24 recombinant protein, we utilized a poly(lactic-co-glycolic acid) nanoparticle delivery system in conjunction with CpG motif-containing oligodeoxynucleotides as an immunomodulatory adjuvant. In a BALB/c mouse model, the vaccine produced a TH1-biased immune response, as demonstrated by a significant increase in antigen-specific IFNγ-producing splenocytes, IgG2a titers, and proliferative capacity of CD8(+) T cells. When tested for therapeutic efficacy, significantly reduced systemic parasitemia was seen during peak parasitemia. Additionally, there was a significant reduction in cardiac parasite burden and inflammatory cell infiltrate. This is the first study demonstrating immunogenicity and efficacy of a therapeutic Chagas vaccine using a nanoparticle delivery system.
Assuntos
Doença de Chagas/terapia , Vacinas Protozoárias/uso terapêutico , Trypanosoma cruzi/imunologia , Vacinas de DNA/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antiprotozoários/imunologia , Linfócitos T CD8-Positivos/imunologia , Cardiomiopatia Chagásica/terapia , Doença de Chagas/imunologia , Modelos Animais de Doenças , Feminino , Coração/parasitologia , Imunidade Celular , Imunoglobulina G/biossíntese , Imunoglobulina G/imunologia , Imunoterapia/métodos , Interferon gama/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas , Oligodesoxirribonucleotídeos/imunologia , Parasitemia/terapia , Vacinas Protozoárias/imunologia , Células Th1/imunologia , Vacinas de DNA/efeitos adversos , Vacinas de DNA/imunologiaRESUMO
Chagas disease, caused by the parasite Trypanosoma cruzi, is an emerging infectious disease in the United States. In our study, 24 out of 39 triatomines, from the specie Triatoma rubida, were infected with T. cruzi. Additionally, only the genotype TcI was characterized among the parasite specimens. Improved knowledge of local epidemiology is needed to prevent transmission of Chagas disease.