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Biomed Res Int ; 2021: 9940010, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34136576

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) infection is a public health epidemic, leading to around 3 million hospitalization and about 66,000 deaths each year. It is a life-threatening condition exclusive to children with no effective treatment. METHODS: In this study, we used system-level and vaccinomics approaches to design a polyvalent vaccine for RSV, which could stimulate the immune components of the host to manage this infection. Our framework involves data accession, antigenicity and subcellular localization analysis, T cell epitope prediction, proteasomal and conservancy evaluation, host-pathogen-protein interactions, pathway studies, and in silico binding affinity analysis. RESULTS: We found glycoprotein (G), fusion protein (F), and small hydrophobic protein (SH) of RSV as potential vaccine candidates. Of these proteins (G, F, and SH), we found 9 epitopes for multiple alleles of MHC classes I and II bear significant binding affinity. These potential epitopes were linked to form a polyvalent construct using AAY, GPGPG linkers, and cholera toxin B adjuvant at N-terminal with a 23.9 kDa molecular weight of 224 amino acid residues. The final construct was a stable, immunogenic, and nonallergenic protein containing cleavage sites, TAP transport efficiency, posttranslation shifts, and CTL epitopes. The molecular docking indicated the optimum binding affinity of RSV polyvalent construct with MHC molecules (-12.49 and -10.48 kcal/mol for MHC classes I and II, respectively). This interaction showed that a polyvalent construct could manage and control this disease. CONCLUSION: Our vaccinomics and system-level investigation could be appropriate to trigger the host immune system to prevent RSV infection.


Assuntos
Biologia Computacional/métodos , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vírus Sincicial Respiratório Humano , Vacinas Combinadas/uso terapêutico , Alelos , Antígenos , Códon , Simulação por Computador , Epitopos , Epitopos de Linfócito T , Glicoproteínas/química , Antígenos de Histocompatibilidade Classe I , Antígenos de Histocompatibilidade Classe II , Hospitalização , Humanos , Sistema Imunitário , Simulação de Acoplamento Molecular , Complexo de Endopeptidases do Proteassoma , Mapeamento de Interação de Proteínas , Proteômica , Linfócitos T/imunologia , Vacinas , Proteínas Virais de Fusão/química
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