Investigação do efeito profilático da imunização com o adenovírus codificando a proteína ASP2, na incidência de ninhos de amastigotas e alterações patológicas nos tecidos de camundongos
Data
2024-08-19
Autores
Dias, Thayza Aires 
Orientadores
Ribeiro, Daniel Araki
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
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Resumo
A doença de Chagas é multifatorial, com envolvimento de inúmeros eventos celulares, moleculares, bioquímicos e fisiológicos que atuam direta ou indiretamente no aparecimento das lesões produzidas por Trypanossoma cruzi (T. cruzi) no hospedeiro vertebrado. O objetivo do estudo foi realizar uma quantificação e mapeamento nos principais tecidos acometidos com a doença de Chagas, compreendendo os achados histopatológicos, durante a infecção por T. cruzi em modelos de camundongos A/Sn. Para tanto, um total de 24 camundongos machos A/Sn, foram distribuídos em 4 grupos, com 6 animais cada: grupo 1 (controle), os animais não foram submetidos a imunização com a AdASP2 ou infecção; grupo 2 Adβgal: os animais foram imunizados por via intranasal (IN) com duas doses da vacina Adβgal, sendo a primeira dose no dia zero e a segunda dose no 21º dia e posteriormente infectados com T. cruzi no 42º dia. Grupo 3 AdASP2 (IN): os animais foram imunizados por via intranasal (IN) com duas doses da vacina AdASP2 sendo a primeira dose no dia zero e a segunda dose no 21º dia e posteriormente infectados com T. cruzi no 42º dia; grupo 4 AdASP2 (IM): os animais foram imunizados por via intramuscular (IM) com duas doses da vacina AdASP2 a primeira dose no dia zero e a segunda dose no 21º dia e posteriormente infectados com T. cruzi no 42º dia; No 57º dia, todos os animais foram eutanasiados e 5 tecidos foram avaliados: cardíaco, gástrico, hepático, tecido do cólon e quadríceps. A imunização de camundongos com adenovírus que codifica a proteína ASP2 resultou em redução significativa da gravidade das alterações histopatológicas e da presença de ninhos de amastigotas nos tecidos cardíaco, gástrico e hepático, em comparação com os animais apenas infectados com T. cruzi. Os tecidos mais susceptíveis à infecção foram coração, fígado e estômago. Com a imunização, foi percebida na diminuição dos ninhos em três dos tecidos analisados nesse estudo. Além disso, o processo de imunização, tanto intramuscular quanto nasal foi eficiente na diminuição das alterações histológicas dos tecidos avaliados nesse estudo. Esses resultados indicam o potencial da vacina com finalidade terapêutica para tratamento da doença de Chagas.
Chagas disease is multifactorial, involving numerous cellular, molecular, biochemical, and physiological events that directly or indirectly contribute to the development of lesions caused by Trypanosoma cruzi (T. cruzi) in the vertebrate host. The aim of this study was to quantify and map the main tissues affected by Chagas disease, analyzing histopathological findings during T. cruzi infection in A/Sn mouse models. A total of 24 male A/Sn mice were divided into four groups, with six animals each: Group 1 - (Control): animals were not subjected to Ad-ASP2 immunization or infection; Group 2 - Ad-βgal: animals were immunized intranasally (IN) with two doses of the Ad-βgal vaccine, the first dose on day zero and the second dose on day 21, followed by infection with T. cruzi on day 42; Group 3 - Ad-ASP2 (IN): animals were immunized intranasally (IN) with two doses of the Ad-ASP2 vaccine, the first dose on day zero and the second dose on day 21, followed by infection with T. cruzi on day 42; Group 4 - Ad-ASP2 (IM): animals were immunized intramuscularly (IM) with two doses of the AdASP2 vaccine, the first dose on day zero and the second dose on day 21, followed by infection with T. cruzi on day 42. On day 57, all animals were euthanized, and five tissues were evaluated: cardiac, gastric, hepatic, colon tissue, and quadriceps. Immunization of mice with adenovirus encoding the ASP2 protein resulted in a significant reduction in the severity of histopathological changes and the presence of amastigote nests in cardiac, gastric, and hepatic tissues compared to animals infected with T. cruzi alone. The most susceptible tissues to infection were the heart, liver, and stomach. Immunization led to a reduction in amastigote nests in three of the tissues analyzed in this study. Furthermore, both intramuscular and nasal immunization were effective in reducing histological changes in the tissues evaluated in this study. These results indicate the potential of the vaccine for therapeutic purposes in the treatment of Chagas disease.
Chagas disease is multifactorial, involving numerous cellular, molecular, biochemical, and physiological events that directly or indirectly contribute to the development of lesions caused by Trypanosoma cruzi (T. cruzi) in the vertebrate host. The aim of this study was to quantify and map the main tissues affected by Chagas disease, analyzing histopathological findings during T. cruzi infection in A/Sn mouse models. A total of 24 male A/Sn mice were divided into four groups, with six animals each: Group 1 - (Control): animals were not subjected to Ad-ASP2 immunization or infection; Group 2 - Ad-βgal: animals were immunized intranasally (IN) with two doses of the Ad-βgal vaccine, the first dose on day zero and the second dose on day 21, followed by infection with T. cruzi on day 42; Group 3 - Ad-ASP2 (IN): animals were immunized intranasally (IN) with two doses of the Ad-ASP2 vaccine, the first dose on day zero and the second dose on day 21, followed by infection with T. cruzi on day 42; Group 4 - Ad-ASP2 (IM): animals were immunized intramuscularly (IM) with two doses of the AdASP2 vaccine, the first dose on day zero and the second dose on day 21, followed by infection with T. cruzi on day 42. On day 57, all animals were euthanized, and five tissues were evaluated: cardiac, gastric, hepatic, colon tissue, and quadriceps. Immunization of mice with adenovirus encoding the ASP2 protein resulted in a significant reduction in the severity of histopathological changes and the presence of amastigote nests in cardiac, gastric, and hepatic tissues compared to animals infected with T. cruzi alone. The most susceptible tissues to infection were the heart, liver, and stomach. Immunization led to a reduction in amastigote nests in three of the tissues analyzed in this study. Furthermore, both intramuscular and nasal immunization were effective in reducing histological changes in the tissues evaluated in this study. These results indicate the potential of the vaccine for therapeutic purposes in the treatment of Chagas disease.
Descrição
Citação
DIAS, Thayza Aires. Investigação do efeito profilático da imunização com o adenovírus codificando a proteína ASP2, na incidência de ninhos de amastigotas e alterações patológicas nos tecidos de camundongos. 2024. 65 f. Dissertação (Mestrado Interdisciplinar em Ciências da Saúde) - Universidade Federal de São Paulo, Instituto de Saúde e Sociedade, Santos, 2024.