CD4+ and CD8+ T-cell multi-epitope chimeric protein associated with an MPLA adjuvant induce protective efficacy and long-term immunological memory for the immunoprophylaxis of American Tegumentary Leishmaniasis.

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Autor(es): dc.creatorMoura, Dênia Monteiro de-
Autor(es): dc.creatorCarvalho, Ana Maria Ravena Severino-
Autor(es): dc.creatorBrito, Rory Cristiane Fortes de-
Autor(es): dc.creatorRoatt, Bruno Mendes-
Autor(es): dc.creatorLage, Daniela Pagliara-
Autor(es): dc.creatorMartins, Vivian Tamietti-
Autor(es): dc.creatorCruz, Luiza dos Reis-
Autor(es): dc.creatorMedeiros, Fernanda Alvarenga Cardoso-
Autor(es): dc.creatorBatista, Sarah Dutra-
Autor(es): dc.creatorPinheiro, Guilherme Rafael Gomide-
Autor(es): dc.creatorRocha, Manoel Otávio da Costa-
Autor(es): dc.creatorCoelho, Eduardo Antônio Ferraz-
Autor(es): dc.creatorDuarte, Mariana Costa-
Autor(es): dc.creatorMendes, Tiago Antônio de Oliveira-
Autor(es): dc.creatorSouza, Daniel Menezes-
Data de aceite: dc.date.accessioned2025-08-21T15:38:19Z-
Data de disponibilização: dc.date.available2025-08-21T15:38:19Z-
Data de envio: dc.date.issued2025-02-21-
Data de envio: dc.date.issued2023-
Fonte completa do material: dc.identifierhttps://www.repositorio.ufop.br/handle/123456789/19772-
Fonte completa do material: dc.identifierhttps://www.sciencedirect.com/science/article/pii/S0264410X24008417-
Fonte completa do material: dc.identifierhttps://doi.org/10.1016/j.vaccine.2024.126178-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/capes/1020365-
Descrição: dc.descriptionAmerican Tegumentary Leishmaniasis (ATL) is a disease of high severity and incidence in Brazil, in addition to being a worldwide concern in public health. Leishmania amazonensis is one of the etiological agents of ATL, and the inefficiency of control measures, associated with the high toxicity of the treatment and the lack of effective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present study proposes to elaborate a chimeric protein (rChiP), based on the fusion of multiple epitopes of CD4+/CD8+ T cells, identified in the immunoproteome of the parasites L. amazonensis and L. braziliensis. The designed chimeric protein was tested in the L. amazonensis murine model of infection using the following formulations: 25 μg of the rChiP in saline (rChiP group) and 25 μg of the rChiP plus 25 μg of MPLA-PHAD® (rChiP+MPLA group). After completing immunization, CD4+ and CD8+ T cells, stimulated with SLa-Antigen or rChiP, showed an increased production of nitric oxide and intracytoplasmic pro-inflammatory cytokines, in addition to the generation of central and effector memory T cells. rChiP and rChiP+MPLA formulations were able to promote an effective protection against L. amazonensis infection determined by a reduction in the development of skin lesions and lower parasitic burden. Reduction in the development of skin lesions and lower parasitic burden in the vaccinated groups were associated with an increase of nitrite, CD4+/CD8+IFN-γ+TNF-α+ and CD4+/CD8+CD44highCD62Lhigh/low T cells, IgGTotal, IgG2a, and lower rates of IgG1 and CD4+/CD8+IL-10+. This data suggests that proposed formulations could be considered potential tools to prevent ATL.-
Formato: dc.formatapplication/pdf-
Idioma: dc.languageen-
Direitos: dc.rightsrestrito-
Palavras-chave: dc.subjectAmerican Tegumentary Leishmaniasis-
Palavras-chave: dc.subjectLeishmania amazonensis-
Palavras-chave: dc.subjectVaccine-
Palavras-chave: dc.subjectImmunoinformatics-
Palavras-chave: dc.subjectT-cell epitope mapping-
Título: dc.titleCD4+ and CD8+ T-cell multi-epitope chimeric protein associated with an MPLA adjuvant induce protective efficacy and long-term immunological memory for the immunoprophylaxis of American Tegumentary Leishmaniasis.-
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