Recombinant Mycobacterium bovis BCG is a promising platform to develop vaccines against Trypansoma cruzi infection
Autor: | Héctor R. Morbidoni, Iván Sergio Marcipar, Gabriel Cabrera, Karen Silva Leal, Ana Bortolotti, Iván Bontempi, Genaro Díaz, Estefanía Prochetto, Odir Antônio Dellagostin, Sibele Borsuk |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Protozoan Vaccines medicine.medical_treatment Trypanosoma cruzi Immunology Protozoan Proteins Neuraminidase Cruzipain Antigens Protozoan Parasitemia 03 medical and health sciences Mice 0302 clinical medicine Immune system Antigen Adjuvants Immunologic Interferon medicine Immunology and Allergy Animals Humans Chagas Disease Cloning Molecular Cells Cultured Mycobacterium bovis Vaccines Synthetic biology Original Articles Th1 Cells biology.organism_classification medicine.disease Virology Cysteine Endopeptidases Disease Models Animal 030104 developmental biology Th17 Cells Immunization Adjuvant 030215 immunology medicine.drug |
Zdroj: | Clin Exp Immunol |
ISSN: | 1365-2249 |
Popis: | Summary Chagas disease, caused by the hemoflagelate parasite Trypanosoma cruzi, is one of the most prevalent endemic parasitoses, affecting 7–8 million people. Due to the complexity of the infection, no vaccines are availabel at present. The extraordinary adjuvant capacity of bacille Calmette–Guérin (BCG) was explored in this work to develop a vaccine candidate to protect against T. cruzi infection using the recombinant BCG (rBCG) vaccine platform. Three antigens of the parasite corresponding to the N and C terminal fragments of the enzyme trans-sialidase (NT-TS and CT-TS, respectively) and a fragment of the cruzipain enzyme (CZf) were cloned into the vectors pUS997 and pUS2000 and transformed into the BCG Pasteur strain. In vaccinated mice, rBCG expressing NT-TS in pUS2000 plasmid provided the highest protection and the lowest parasitemia after challenging BALB/c mice with a 50% lethal dose of parasites. When mice vaccinated with pUS2000-NT-TS were challenged with a 100% lethal dose of parasite, high levels of protection were also obtained, together with a low degree of cardiac lesions 120 days after infection. In immunized mice with pUS2000-NT-TS/rBCG clone, the proliferation of CD4+ cells from splenocytes stimulated with the TS antigen was significant; this stimulation increased interferon (IFN)-γ and interleukin (IL)-17 within CD4⁺ T lymphocytes (LTCD4+) cells and IFN-γ and CD107 expression within LTCD8+ cells. Therefore, pUS2000-NT-TS/rBCG conferred high levels of protection, which correlated with an immune response orientated towards a T helper type 1 (Th1)/Th17 profile, together with an LTC-specific response, indicating that rBCG is a promising platform to develop vaccines against T. cruzi. |
Databáze: | OpenAIRE |
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