Rational selection of immunodominant and preserved epitope Sm043300e from Schistosoma mansoni and design of a chimeric molecule for biotechnological purposes

Autor: Cristina Toscano Fonseca, Alex Guterres Taranto, Débora de Oliveira Lopes, Luciana Lara dos Santos, Maria Juliana Ferreira Passos, Marcelo Donizete Lopes, José A.F.P. Villar, Cláudia de Souza, Flávio Martins de Oliveira, Moacyr Comar Junior, Bruna Franciele Faria, Laís Cunha Grossi Ferreira
Rok vydání: 2017
Předmět:
0301 basic medicine
CD4-Positive T-Lymphocytes
Models
Molecular
Protein Conformation
In silico
Recombinant Fusion Proteins
030231 tropical medicine
Immunology
Antibodies
Helminth
Drug Evaluation
Preclinical
Lymphocyte proliferation
Biology
Lymphocyte Activation
Epitope
Receptors
G-Protein-Coupled
03 medical and health sciences
Mice
0302 clinical medicine
Animals
Combinatorial Chemistry Techniques
Humans
Amino Acid Sequence
Molecular Biology
Vaccines
Synthetic
Immunodominant Epitopes
Reverse vaccinology
Histocompatibility Antigens Class II
Membrane Proteins
Helminth Proteins
Schistosoma mansoni
biology.organism_classification
Virology
Transmembrane protein
Schistosomiasis mansoni
Mice
Inbred C57BL
Molecular Docking Simulation
030104 developmental biology
Membrane protein
Antigens
Helminth
Drug Design
Vaccines
Subunit
biology.protein
Schistosoma haematobium
Female
Antibody
Sequence Alignment
HLA-DRB1 Chains
Zdroj: Molecular immunology. 93
ISSN: 1872-9142
Popis: Human schistosomiasis is a neglected tropical disease of great importance in public health. A large number of people are infected with schistosomiasis, making vaccine development and effective diagnosis important control strategies. A rational epitope prediction workflow using Schistosoma mansoni hypothetical proteins was previously presented by our group, and an improvement to that approach is presented here. Briefly, immunodominant epitopes from parasite membrane proteins were predicted by reverse vaccinology strategy with additional in silico analysis. Furthermore, epitope recognition was evaluated using sera of individuals infected with S. mansoni. The epitope that stood out in both in silico and in vitro assays was used to compose a rational chimeric molecule to improve immune response activation. Out of 2185 transmembrane proteins, four epitopes with high binding affinities for human and mouse MHCII molecules were selected through computational screening. These epitopes were synthesized to evaluate their ability to induce TCD4+ lymphocyte proliferation in mice. Sm204830e and Sm043300e induced significant TCD4+ proliferation. Both epitopes were submitted to enzyme-linked immunosorbent assay to evaluate their recognition by IgG antibodies from the sera of infected individuals, and epitope Sm043300 was significantly recognized in most sera samples. Epitope Sm043300 also showed good affinity for human MHCII molecules in molecular docking, and its sequence is curiously highly conserved in four S. mansoni proteins, all of which are described as G-protein-coupled receptors. In addition, we have demonstrated the feasibility of incorporating this epitope, which showed low similarity to human sequences, into a chimeric molecule. The stability of the molecule was evaluated by molecular modeling aimed at future molecule production for use in diagnosis and vaccination trials.
Databáze: OpenAIRE
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