Development of an immunogen containing CD4+/CD8+ T-cell epitopes for the prophylaxis of tegumentary leishmaniasis

• Published in: Applied microbiology and biotechnology 2022-06, Vol.106 (12), p.4627-4641
• Main Authors: de Andrade Ferraz, Isabela, Carvalho, Ana Maria Ravena Severino, de Brito, Rory Cristiane Fortes, Roatt, Bruno Mendes, Martins, Vívian Tamietti, Lage, Daniela Pagliara, dos Reis Cruz, Luiza, Medeiros, Fernanda Alvarenga Cardoso, Gonçalves, Denise Utsch, da Costa Rocha, Manoel Otávio, Coelho, Eduardo Antonio Ferraz, de Oliveira Mendes, Tiago Antônio, Duarte, Mariana Costa, Menezes-Souza, Daniel
• Format: Article
• Language: English
• Subjects: Applied Genetics and Molecular Biotechnology; Biomarkers; Biomedical and Life Sciences; Biotechnology; CD4 antigen; CD8 antigen; Epitopes; Etiology; Host-parasite interactions; Immunization; Immunoglobulin G; Immunological memory; Immunology; Interleukin 10; Life Sciences; Lymphocytes T; Memory cells; Microbial Genetics and Genomics; Microbiology; Parasites; Parasitic diseases; Prophylaxis; Proteins; Tegumentary leishmaniasis; Toxicity; Tumor necrosis factor-α; Vaccine development; Vaccines; Vector-borne diseases; γ-Interferon
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-022-12033-7

Tegumentary leishmaniasis (TL) is a disease of high severity and incidence in Brazil, and Leishmania braziliensis is its main etiological agent. The inefficiency of control measures, such as high toxicity and costs of current treatments and the lack of effective 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 ( r MEP/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: r MEP/TL in saline or associated with MPLA-PHAD ® . Our data revealed that, after immunization (three doses; 14-day intervals) and subsequent challenging, r MEP/TL and r MEP/TL + MPLA-vaccinated mice showed an increased production of key immunological biomarkers of protection, such as IgG 2a , IgG 2a /IgG 1 , 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 (CD44 high CD62L high ) and effector (CD44 high CD62L low ) memory of CD4 + and CD8 + T-cells. These findings, associated with the observation of lower rates of parasite burdens in the vaccinated groups, when compared to the control groups, suggest that immunization with r MEP/TL and, preferably, associated with an adjuvant, may be considered an effective tool to prevent TL. Key points • Rational design approaches for vaccine development. • Central and effector memory of CD4+ and CD8+ T-cells. • Vaccine comprised of rMEP/TL plus MPLA as an effective tool to prevent TL.