Combination of In Silico Methods in the Search for Potential CD4(+) and CD8(+) T Cell Epitopes in the Proteome of Leishmania braziliensis.
The leishmaniases are neglected tropical diseases widespread throughout the globe, which are caused by protozoans from the genus Leishmania and are transmitted by infected phlebotomine flies. The development of a safe and effective vaccine against these diseases has been seen as the best alternative to control and reduce the number of cases. To support vaccine development, this work has applied an in silico approach to search for high potential peptide epitopes able to bind to different major histocompatibility complex Class I and Class II (MHC I and MHC II) molecules from different human populations. First, the predicted proteome of Leishmania braziliensis was compared and analyzed by modern linear programs to find epitopes with the capacity to trigger an immune response. This approach resulted in thousands of epitopes derived from 8,000 proteins conserved among different Leishmania species. Epitopes from proteins similar to those found in host species were excluded, and epitopes from proteins conserved between different Leishmania species and belonging to surface proteins were preferentially selected. The resulting epitopes were then clustered, to avoid redundancies, resulting in a total of 230 individual epitopes for MHC I and 2,319 for MHC II. These were used for molecular modeling and docking with MHC structures retrieved from the Protein Data Bank. Molecular docking then ranked epitopes based on their predicted binding affinity to both MHC I and II. Peptides corresponding to the top 10 ranked epitopes were synthesized and evaluated in vitro for their capacity to stimulate peripheral blood mononuclear cells (PBMC) from post-treated cutaneous leishmaniasis patients, with PBMC from healthy donors used as control. From the 10 peptides tested, 50% showed to be immunogenic and capable to stimulate the proliferation of lymphocytes from recovered individuals.
Department of Natural Sciences, Universidade de Pernambuco, Garanhuns, Pernambuco, Brazil; Department of Immunology, Fundação Oswaldo Cruz, Recife, Pernambuco, Brazil.
Rafael de Freitas
Rde F
E Silva
Department of Pharmaceutical Sciences, Universidade Federal de Pernambuco , Recife, Pernambuco , Brazil.
Luiz Felipe Gomes Rebello
LF
Ferreira
Department of Pharmaceutical Sciences, Universidade Federal de Pernambuco , Recife, Pernambuco , Brazil.
Marcelo Zaldini
MZ
Hernandes
Department of Immunology, Fundação Oswaldo Cruz , Recife, Pernambuco , Brazil.
Maria Edileuza Felinto
ME
de Brito
Department of Immunology, Fundação Oswaldo Cruz , Recife, Pernambuco , Brazil.
Beatriz Coutinho
BC
de Oliveira
Department of Immunology, Fundação Oswaldo Cruz , Recife, Pernambuco , Brazil.
Ailton Alvaro
AA
da Silva
Department of Microbiology, Fundação Oswaldo Cruz , Recife, Pernambuco , Brazil.
Osvaldo Pompílio
OP
de-Melo-Neto
Department of Microbiology, Fundação Oswaldo Cruz , Recife, Pernambuco , Brazil.
Antônio Mauro
AM
Rezende
Department of Immunology, Fundação Oswaldo Cruz , Recife, Pernambuco , Brazil.
Valéria Rêgo Alves
VR
Pereira
CD4+ CD8+ T cell epitopes; Leishmania braziliensis; cutaneous leishmaniasis; neglected tropical diseases; vaccine development