title: The Use of Reverse Vaccinology and Molecular Modeling Associated with Cell Proliferation Stimulation Approach to Select Promiscuous Epitopes from Schistosoma mansoni.
abstract: Schistosomiasis remains an important parasitic disease that affects millions of individuals worldwide. Despite the availability of chemotherapy, the occurrence of constant reinfection demonstrates the need for additional forms of intervention and the development of a vaccine represents a relevant strategy to control this disease. With the advent of genomics and bioinformatics, new strategies to search for vaccine targets have been proposed, as the reverse vaccinology. In this work, computational analyses of Schistosoma mansoni membrane proteins were performed to predict epitopes with high affinity for different human leukocyte antigen (HLA)-DRB1. Ten epitopes were selected and along with murine major histocompatibility complex (MHC) class II molecule had their three-dimensional structures optimized. Epitope interactions were evaluated against murine MHC class II molecule through molecular docking, electrostatic potential, and molecular volume. The epitope Sm141290 and Sm050890 stood out in most of the molecular modeling analyses. Cellular proliferation assay was performed to evaluate the ability of these epitopes to bind to murine MHC II molecules and stimulate CD4+ T cells showing that the same epitopes were able to significantly stimulate cell proliferation. This work showed an important strategy of peptide selection for epitope-based vaccine design, achieved by in silico analyses that can precede in vivo and in vitro experiments, avoiding excessive experimentation.
authors.affiliation: Laboratory of Molecular Biology, Universidade Federal de São João del Rei, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501-296, Brazil.
authors.forename: Flávio M
authors.initials: FM
authors.lastname: Oliveira
authors.affiliation: Laboratory of Molecular Modeling, Universidade Federal de São João del Rei, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501-296, Brazil.
authors.forename: Ivan E V
authors.initials: IE
authors.lastname: Coelho
authors.affiliation: Laboratory of Molecular Biology, Universidade Federal de São João del Rei, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501-296, Brazil.
authors.forename: Marcelo D
authors.initials: MD
authors.lastname: Lopes
authors.affiliation: Laboratory of Molecular Modeling, Universidade Federal de São João del Rei, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501-296, Brazil.
authors.forename: Alex G
authors.initials: AG
authors.lastname: Taranto
authors.affiliation: Laboratory of Molecular Modeling, Universidade Federal de São João del Rei, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501-296, Brazil.
authors.forename: Moacyr C
authors.initials: MC
authors.lastname: Junior
authors.affiliation: Laboratory of Molecular Biology, Universidade Federal de São João del Rei, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501-296, Brazil.
authors.forename: Luciana L D
authors.initials: LL
authors.lastname: Santos
authors.affiliation: Laboratory of Molecular Biology, Universidade Federal de São João del Rei, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501-296, Brazil.
authors.forename: José A P F
authors.initials: JA
authors.lastname: Villar
authors.affiliation: Research Group in Parasite Biology and Immunology, Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz, Av. Augusto de Lima, Belo Horizonte, MG, 30190-002, Brazil.
authors.forename: Cristina T
authors.initials: CT
authors.lastname: Fonseca
authors.affiliation: Laboratory of Molecular Biology, Universidade Federal de São João del Rei, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, Minas Gerais, 35501-296, Brazil. debora@ufsj.edu.br.
authors.forename: Débora D O
authors.initials: DD
authors.lastname: Lopes
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics*; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D012550:Schistosoma mansoni / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000235:genetics / Q000276:immunology*
chemical_list: D000939:Epitopes; D008565:Membrane Proteins; D014612:Vaccines
keywords: Cell proliferation; Epitopes; Molecular docking; Reverse vaccinology; Schistosomiasis