Designing of Potential Polyvalent Vaccine Model for Respiratory Syncytial Virus by System Level Immunoinformatics Approaches

Abstract

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.

Experimental trials of predicted CD4+ and CD8+ T-cell epitopes of respiratory syncytial virus

“…The functional annotation of the screened proteins as a protein-protein interaction was given in the supplementary data ( Supplementary Figure S2 ). The results of proteasomal cleavage of screened proteins were given in our previous study ( 23 ).…”

“…Based on the antigenicity of the epitopes and their binding energies with the target alleles CD4 + and CD8 + , such as HLA-A*01:01 for CD8 + (PDB ID: 1w72) and HLA-DRA/DRB1*01:01 for CD4 + (PDB ID: 1BX2), six epitopes were selected for further in-vivo experimentation ( Table 2 ). Molecular interaction images along with binding energy values are provided as supplementary data ( Supplementary Figures S3 – S5 ) from our previously published paper ( 23 ). The physicochemical properties of the selected epitopes such as instability index, charge, toxin prediction, SVM score, hydropathicity, pI value, and aliphatic index were investigated ( Table 3 ).…”

“…Protein sequences, in FASTA format for the RSV strain type A, were retrieved from the NCBI and Uniprot databases. These proteins were further screened based on molecular weight, antigenicity (threshold level 0.45), and subcellular localization to predict the T-cell epitopes ( 23 ). The protein-to-protein interaction network of antigenic RSV proteins with other host proteins was generated by Cytoscape version 3.6 ( 24 ).…”

Exploring different virulent proteins of human respiratory syncytial virus for designing a novel epitope-based polyvalent vaccine: Immunoinformatics and molecular dynamics approaches

“…The EAAAK linkers have a viable partition of bifunctional fusion protein domains [72], while the GPGPG linkers are ideal for preventing junctional epitope production and optimizing the processing and presentation of the immune system [73]. The AAY linker is also commonly used in the design trials of the in silico vaccine since this linker offers successful and efficient epitope conjugation [74]. In addition, bi-lysine (KK) linkers are active in the autonomous immunological function of vaccine epitopes [75].…”

Mapping Potential Vaccine Candidates Predicted by VaxiJen for Different Viral Pathogens between 2017–2021—A Scoping Review

“…Shrimp white spot syndrome virus (WSSV) [303] Mayaro virus (MAYV) [304,305] 2 Sin Nombre virus (SNV) [306] Newcastle disease virus (NDV) [307,308] 2 Smallpox viruses [309] Respiratory syncytial virus (RSV) [310,311] 2 Tick-borne encephalitis virus (TBEV) [312] Rift Valley fever virus [313,314] 2 Yellow fever virus (YFV) [315] Boldface denotes the top three pathogens with the highest number of publications. The table is sorted by number of publications descending, then by pathogen ascending.…”