A recombinant chimeric protein composed of human and mice‐specific CD4+ and CD8+ T‐cell epitopes protects against visceral leishmaniasis

• Published in: Parasite immunology 2017-01, Vol.39 (1), p.n/a
• Main Authors: Martins, V. T., Duarte, M. C., Lage, D. P., Costa, L. E., Carvalho, A. M. R. S., Mendes, T. A. O., Roatt, B. M., Menezes‐Souza, D., Soto, M., Coelho, E. A. F.
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Animal models; Animals; Antibodies; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Epitopes; Epitopes, T-Lymphocyte - immunology; Female; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Haplotypes; Humans; immune response; Immunogenicity, Vaccine; Immunoglobulin G; Interleukin 10; Interleukin 12; Interleukin 4; Interleukin-10 - metabolism; Interleukin-12 - metabolism; Interleukin-4 - metabolism; Leishmania infantum; Leishmania infantum - immunology; Leishmaniasis Vaccines - genetics; Leishmaniasis Vaccines - immunology; Leishmaniasis, Visceral - prevention & control; Lymphocytes T; Mice; Mice, Inbred BALB C; Nitrites; Parasitic diseases; Polymerase chain reaction; recombinant chimeric protein; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Rodents; Saponins - immunology; T‐cell epitopes; vaccine; Vaccines; Vaccines, Synthetic - immunology; Visceral leishmaniasis
• ISSN: 0141-9838; 1365-3024
• DOI: 10.1111/pim.12359

Summary In this study, a recombinant chimeric protein (RCP), which was composed of specific CD4+ and CD8+ T‐cell epitopes to murine and human haplotypes, was evaluated as an immunogen against Leishmania infantum infection in a murine model. BALB/c mice received saline were immunized with saponin or with RCP with or without an adjuvant. The results showed that RCP/saponin‐vaccinated mice presented significantly higher levels of antileishmanial IFN‐γ, IL‐12 and GM‐CSF before and after challenge, which were associated with the reduction of IL‐4 and IL‐10 mediated responses. These animals showed significant reductions in the parasite burden in all evaluated organs, when both limiting dilution and quantitative real‐time PCR techniques were used. In addition, the protected animals presented higher levels of parasite‐specific nitrite, as well as the presence of anti‐Leishmania IgG2a isotype antibodies. In conclusion, the RCP/saponin vaccine could be considered as a prophylactic alternative to prevent against VL.