Protective immunity triggered by ectonucleoside triphosphate diphosphohydrolase-based biopharmaceuticals attenuates cardiac parasitism and prevents mortality in Trypanosoma cruzi infection
| Autor: | Alessandra Teixeira, Paula, Karla Veloso Gonçalves, Ribeiro, Kimberly Freitas, Cardoso, Daniel Silva Sena, Bastos, Eliziária Cardoso, Santos, Rômulo Dias, Novaes, Silvia Almeida, Cardoso, Leandro Licursi, Oliveira |
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| Rok vydání: | 2022 |
| Předmět: |
Biological Products
Mice Inbred BALB C Antiparasitic Agents Interleukin-6 Tumor Necrosis Factor-alpha Trypanosoma cruzi Interleukin-17 Organic Chemistry Clinical Biochemistry Pharmaceutical Science Nucleosides Biochemistry Recombinant Proteins Interleukin-10 Mice Polyphosphates Drug Discovery Animals Molecular Medicine Chagas Disease Molecular Biology |
| Zdroj: | Bioorganic & Medicinal Chemistry. 72:116966 |
| ISSN: | 0968-0896 |
| DOI: | 10.1016/j.bmc.2022.116966 |
| Popis: | Chagas disease is a potentially fatal infection in 21 endemic Latin America countries for which the effectiveness of reference antiparasitic chemotherapy is limited. Thus, we developed three biopharmaceuticals and evaluated the effectiveness of different immunization strategies (recombinant protein NTPDase-1 [rNTPDase-1], DNA plasmid encoding Trypanosoma cruzi NTPDase-1 [TcNTPDase-1] and DNA-NTPDase-1 prime/rNTPDase-1 boost [Prime-boost]) based on the surface ecto-nucleoside triphosphate diphosphohydrolase (ecto-NTPDase) enzyme of T. cruzi in animals challenged with a virulent strain (Y) of this parasite. BALB/c mice were immunized three times at 30 days intervals, challenged with T. cruzi 15 days after the last immunization, and euthanized 30 days after T. cruzi challenge. Our results showed limited polarization of specific anti-ecto-NTPDase immunoglobulins in mice receiving both immunization protocols. Conversely, the Prime-boost strategy stimulated the Th1 protective phenotype, upregulating TNF-α and downregulating IL-10 production while increasing the activation/distribution of CD3 |
| Databáze: | OpenAIRE |
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