Avaliação do potencial imunogênico e protetor de duas estratégias vacinais contra doença de Chagas: DNA codificando NTPDase-1 e NTPDase-1 recombinante em fêmeas de camundongos BALB/c

A doença de Chagas é causada pelo protozoário hemoflagelado Trypanosoma cruzi. Hospedeiros mamíferos são normalmente infectados através do contato de fezes contaminadas do vetor triatomíneo com feridas na pele, conjuntiva e membranas mucosas oral e nasal. O Benznidazol é o único medicamento para tra...

Nível de Acesso:openAccess
Publication Date:2018
Main Author: Ribeiro, Karla Veloso Gonçalves lattes
Orientador/a: Oliveira, Leandro Licursi de
Format: Tese
Language:por
Published: Universidade Federal de Viçosa
Áreas de Conhecimento:
Online Access:http://www.locus.ufv.br/handle/123456789/24333
Citação:RIBEIRO, Karla Veloso Gonçalves. Avaliação do potencial imunogênico e protetor de duas estratégias vacinais contra doença de Chagas: DNA codificando NTPDase-1 e NTPDase-1 recombinante em fêmeas de camundongos BALB/c. 2018. 47 f. Tese (Doutorado em Biologia Celular e Estrutural) - Universidade Federal de Viçosa, Viçosa. 2018.
Resumo inglês:Chagas disease is caused by haemoflagellated protozoan Trypanosoma cruzi. Mammal hosts are ordinarily infected through of contact of the triatomine vector-contaminated feces with skin breaks, conjunctiva, oral and nasal mucosa. Benznidazole is the only drug to treat the disease in Brazil however it has several side effects and is effective only in the acute phase. Although vector transmission is the predominant mechanism, oral transmission has become common in Brazil. In view of the increase in the number of non-vector cases of disease transmission, in addition to the late or absent diagnosis and toxicity of the available drug, it is extremely important to develop an effective and safe vaccine for disease control. Thus, the aim of the work was to evaluate the immune response induced by recombinant DNA vaccine encoding T. cruzi NTPDase-1 (DNA/NTPDase-1) and recombinant NTPDase-1 vaccine in BALB/c mice. The immunization with the recombinant protein induced faster production of total specific IgG and higher levels of IgG1 and IgG2a compared to DNA/NTPDase-1 vaccine. The T cell profile showed a similar frequency of CD3 + /CD4 + and CD3 + /CD8 + between the protein, DNA and control groups. There was an increased frequency of activated T cells (CD4 + /CD44 + e CD8 + /CD44 + ) in rNTPDase-1 vaccinated group compared to the control and DNA/NTPDase-1 groups. The level of Th1 cytokines (TNF-α and IFN-γ) did not differ between the vaccinated groups, while the level of Th2 cytokines (IL-6 and IL-10) was lower in the DNA and recombinant protein groups compared to the control. The nitric oxide (NO) level increased in immunized mice with recombinant protein. After the challenge, we observed immunization with DNA/NTPDase-1 reduced parasite burden in cardiac tissue when compared to the control and rNTPDase-1 groups. Moreover we observed 100% survival on both vaccinated groups, while 50% of the animals died in the control group. Therefore, the stimulus for specific antibody production, the activation of CD4 + and CD8 + T cells, reduction in the production of anti-inflammatory cytokines and increase of NO production in the vaccine scheme using rNTPDasse-1 protein and the reduction of parasitic load in the cardiac tissue induced by DNA/NTPDase-1 demonstrate the potential of this antigen for the development of vaccine for the control of Chagas ́s disease.