Dados do Trabalho

Título

A computational biology strategy for the design, QM/MM validation, and immune response simulation of a multi-epitope vaccine using the proteome of Yellow Fever virus

Introdução

Frequent outbreaks of yellow fever (YF) are observed, particularly in areas where the disease is endemic. The management of this arbovirus has been questioned due to the lack of a recognized treatment for this condition. The most effective method of defense is the attenuated virus vaccine; however, some populations are discouraged from using it due to possible adverse effects.

Objetivo (s)

The main of this work was develop a multiepitope vaccine capable of triggering an efficient immunological response using immunoinformatics and molecular modelling methods.

Material e Métodos

B- and T-cell epitopes were predicted using the sequences of all structural (E, prM, and C) and nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) proteins from 385 strains of the YF virus. Molecular Dynamics (DM) and Quantum Mechanics/Molecular Mechanics (QM/MM) simulations were employed to enhance the accuracy of docking calculations, with the QM portion of the simulations carried out utilizing the density functional theory formalism (DFT).

Resultados e Conclusão

Ten T- lymphocyte cytotoxic (LTC) and five T-helper (LTH) epitopes were found to overlap with B-lymphocyte epitopes (LB) after assessing the number of human leukocyte antigen (HLA) system alleles for which these epitopes have affinity and testing for antigenicity, immunogenicity, allergenicity, toxicity, and conservation. These epitopes were linked to an adjuvant (ß-defensin) and to each other using ligands, resulting in a vaccine sequence with appropriate physicochemical properties. The 3D structure of this sequence was created, improved, and quality checked; then it was anchored to the Toll-like receptor (TLR-2). Moreover, the inoculation model was able to provide an optimal codon sequence that was inserted into the pET-28a(+) vector for in silico cloning and could even stimulate highly relevant humoral and cellular immunological responses. Overall, these results suggest that the designed multi-epitope vaccine can function as prophylaxis against the yellow fever virus in at-risk populations without causing a significant number of adverse effects. Preclinical research is still required to confirm the computational predictions.

Palavras-chave

Yellow Fever, Multi-epitope vaccine, Immunoinformatics, B-lymphocyte, Cytotoxic T-lymphocyte, Helper T-lymphocyte