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

American 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 th...

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Published in:	Vaccine Vol. 42; no. 21; p. 126178
Main Authors:	Moura, Dênia Monteiro de, Carvalho, Ana Maria Ravena Severino, Brito, Rory Cristiane Fortes de, Roatt, Bruno Mendes, Lage, Daniela Pagliara, Martins, Vivian Tamietti, Cruz, Luiza dos Reis, Medeiros, Fernanda Alvarenga Cardoso, Batista, Sarah Dutra, Pinheiro, Guilherme Rafael Gomide, da Costa Rocha, Manoel Otávio, Coelho, Eduardo Antonio Ferraz, Duarte, Mariana Costa, Mendes, Tiago Antônio de Oliveira, Menezes-Souza, Daniel
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier Ltd 30-08-2024 Elsevier Limited
Subjects:	Adjuvants Adjuvants, Immunologic - administration & dosage American Tegumentary Leishmaniasis Animal models Animals Antibodies, Protozoan - immunology Antigens Antigens, Protozoan - immunology CD4 antigen CD4-Positive T-Lymphocytes - immunology CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell fusion Chimeric protein Chromatography Cytokines - immunology Cytokines - metabolism Disease control Disease Models, Animal Effectiveness Effector cells Epitopes Epitopes, T-Lymphocyte - immunology Etiology Female Fusion protein Immunization Immunoglobulin G Immunoinformatics Immunologic Memory Immunological memory Immunology Immunoprophylaxis Leishmania amazonensis Leishmania braziliensis - immunology Leishmaniasis Vaccines - immunology Leishmaniasis, Cutaneous - immunology Leishmaniasis, Cutaneous - prevention & control Lesions Lipid A - analogs & derivatives Lipid A - immunology Lymphocytes Lymphocytes T Memory cells Mice Mice, Inbred BALB C Nitric oxide Parasites Parasitic diseases Proteins Protozoa Public health Reagents Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - immunology Skin diseases Skin lesions T-cell epitope mapping Tegumentary leishmaniasis Toxicity Tumor necrosis factor-α Vaccine Vaccines Vector-borne diseases γ-Interferon Brazil United States > US American Tegumentary Leishmaniasis T-cell epitope mapping Vaccine Chimeric protein Leishmania amazonensis Immunoinformatics
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Summary:	American 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. [Display omitted] •Rational strategy to develop antigens.•Integration between immunoproteomic and immunoinformatics analyses.•Chimeric protein shows high performance in ATL diagnosis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0264-410X 1873-2518 1873-2518
DOI:	10.1016/j.vaccine.2024.126178