RT Journal Article
SR Electronic
T1 Exploring different virulent proteins of human respiratory syncytial virus for designing a novel epitope-based polyvalent vaccine: Immunoinformatics and molecular dynamics approaches
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.02.02.478791
DO 10.1101/2022.02.02.478791
A1 Abu Tayab Moin
A1 Md. Asad Ullah
A1 Rajesh B. Patil
A1 Nairita Ahsan Faruqui
A1 Bishajit Sarkar
A1 Yusha Araf
A1 Sowmen Das
A1 Khaza Md. Kapil Uddin
A1 Md Shakhawat Hossain
A1 Md. Faruque Miah
A1 Mohammad Ali Moni
A1 Dil Umme Salma Chowdhury
A1 Saiful Islam
YR 2022
UL http://biorxiv.org/content/early/2022/02/02/2022.02.02.478791.abstract
AB Human Respiratory Syncytial Virus (RSV) is one of the most prominent causes of lower respiratory tract infections (LRTI), contributory to infecting people from all age groups - a majority of which comprises infants and children. The implicated severe RSV infections lead to numerous deaths of multitudes of the overall population, predominantly the children, every year. Consequently, despite several distinctive efforts to develop a vaccine against the RSV as a potential countermeasure, there is no approved or licensed vaccine available yet, to control the RSV infection effectively. Therefore, through the utilization of immunoinformatics tools, a computational approach was taken in this study, to design and construct a multi-epitope polyvalent vaccine against the RSV-A and RSV-B strains of the virus. Potential predictions of the T-cell and B-cell epitopes were followed by extensive tests of antigenicity, allergenicity, toxicity, conservancy, homology to human proteome, transmembrane topology, and cytokine-inducing ability. The most promising epitopes (i.e. 13 CTL epitopes, 9 HTL epitopes, and 10 LBL epitopes) exhibiting full conservancy were then selected for designing the peptide fusion with appropriate linkers, having hBD-3 as the adjuvant. The peptide vaccine was modeled, refined, and validated to further improve the structural attributes. Following this, molecular docking analysis with specific TLRs was carried out which revealed excellent interactions and global binding energies. Additionally, molecular dynamics (MD) simulation was conducted which ensured the stability of the interactions between vaccine and TLR. Furthermore, mechanistic approaches to imitate and predict the potential immune response generated by the administration of vaccines were determined through immune simulations. Owing to an overall evaluation, in silico cloning was carried out in efforts to generate recombinant pETite plasmid vectors for subsequent mass production of the vaccine peptide, incorporated within E.coli. However, more in vitro and in vivo experiments can further validate its efficacy against RSV infections.Competing Interest StatementThe authors have declared no competing interest.