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Título: | Development of an immunogen containing CD4+/CD8+ T‐cell epitopes for the prophylaxis of tegumentary leishmaniasis. |
Autor(es): | Ferraz, Isabela de Andrade Carvalho, Ana Maria Ravena Severino Brito, Rory Cristiane Fortes de Roatt, Bruno Mendes Martins, Vivian Tamietti Lage, Daniela Pagliara Cruz, Luiza dos Reis Medeiros, Fernanda Alvarenga Cardoso Gonçalves, Denise Utsch Rocha, Manoel Otávio da Costa Coelho, Eduardo Antônio Ferraz Mendes, Tiago Antônio de Oliveira Duarte, Mariana Costa Souza, Daniel Menezes |
Palavras-chave: | Leishmania braziliensis Vaccine Immunoinformatics T-cell epitope mapping Chimeric protein |
Data do documento: | 2022 |
Referência: | FERRAZ, I. de A. et al. Development of an immunogen containing CD4+/CD8+ T‐cell epitopes for the prophylaxis of tegumentary leishmaniasis. Applied Microbiology and Biotechnology, v. 106, p. 4627-4641, 2022. Disponível em: <https://link.springer.com/article/10.1007/s00253-022-12033-7>. Acesso em: 01 ago. 2023. |
Resumo: | Tegumentary leishmaniasis (TL) is a disease of high severity and incidence in Brazil, and Leishmania braziliensis is its main etiological agent. The inefciency of control measures, such as high toxicity and costs of current treatments and the lack of efective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present work developed a gene encoding multiple T-cell (CD4+/CD8+) epitope, derived from conserved proteins found in Leishmania species and associated with TL, to generate a chimeric protein (rMEP/TL) and compose a vaccine formulation. For this, six T-cell epitopes were selected by immunoinformatics approaches from proteins present in the amastigote stage and associated with host-parasite interactions. The following formulations were then tested in an L. braziliensis murine infection model: rMEP/TL in saline or associated with MPLA-PHAD®. Our data revealed that, after immunization (three doses; 14-day intervals) and subsequent challenging, rMEP/TL and rMEP/TL+MPLA-vaccinated mice showed an increased production of key immunological biomarkers of protection, such as IgG2a, IgG2a/IgG1, NO, CD4+, and CD8+ T-cells with IFN-γ and TNF-α production, associated with a reduction in CD4+IL-10+ and CD8+IL-10+ T-cells. Vaccines also induced the development of central (CD44highCD62Lhigh) and efector (CD44highCD62Llow) memory of CD4+ and CD8+ T-cells. These fndings, associated with the observation of lower rates of parasite burdens in the vaccinated groups, when compared to the control groups, suggest that immunization with rMEP/TL and, preferably, associated with an adjuvant, may be considered an efective tool to prevent TL. |
URI: | http://www.repositorio.ufop.br/jspui/handle/123456789/17699 |
Link para o artigo: | https://link.springer.com/article/10.1007/s00253-022-12033-7 |
DOI: | https://doi.org/10.1007/s00253-022-12033-7 |
ISSN: | 1432-0614 |
Aparece nas coleções: | DECBI - Artigos publicados em periódicos |
Arquivos associados a este item:
Arquivo | Descrição | Tamanho | Formato | |
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ARTIGO_DevelopmentImmunogenContaining.pdf Restricted Access | 1,67 MB | Adobe PDF | Visualizar/Abrir |
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