Abstract
In recent years, epitope-based peptides have constituted a prominent and prospective class in pharmacology; especially in mounting specific immune responses against pathogenic agents. Respiratory Syncytial Virus (RSV) has been a leading cause of mortality in infants and children aged under 5 years. To date, there is a dearth of vaccines or small molecules targeting RSV. The identification of RSV B-cell epitopes is a preliminary step in developing an epitope-based vaccine design. The prediction for B-cell epitopes using an in-silico approach will enhance our understanding of etiopathogenesis and aid in the creation of effective vaccines that target B-cell response. In our study, three distinct prediction tools- ABCpred, Bepipred, and BCpred were used to assess the RSV proteomes, leading to the prediction of 3,314 B-cell epitopes, from which 128 were revealed to be overlapping epitopes. The physicochemical properties of 128 overlapping epitopes were studied subsequently. A total of 35/128 of them were anticipated to be antigenic, non-allergenic, non-toxic, and non-homologous peptides. According to structural analysis utilizing the Ellipro database, 133 linear epitopes and 53 discontinuous epitopes were predicted. Finally, 4 potent epitopes show a high binding score of 0.819 to 0.838, which will improve and strengthen the development of effective RSV vaccines.
Similar content being viewed by others
Data availability
All data supporting this study is provided as supplementary information accompanying this paper.
Abbreviations
- RSV:
-
Human respiratory syncytial virus
- BLAST:
-
Basic Local Alignment Search Tool
- ViPR:
-
Database, Virus Pathogen Database and Analysis Resource
References
Abdulla F, Nain Z, Hossain MM et al (2021) A comprehensive screening of the whole proteome of hantavirus and designing a multi-epitope subunit vaccine for cross-protection against hantavirus: structural vaccinology and immunoinformatics study. Microb Pathog 150:104705. https://doi.org/10.1016/j.micpath.2020.104705
Alix AJP (1999) Predictive estimation of protein linear epitopes by using the program PEOPLE. Vaccine 18:311–314
Amat-ur-Rasool H, Saghir A, Idrees M (2015) Computational prediction and analysis of envelop glycoprotein epitopes of DENV-2 and DENV-3 pakistani isolates: a first step towards Dengue vaccine development. PLoS ONE 10:e0119854
Battles MB, McLellan JS (2019) Respiratory syncytial virus entry and how to block it. Nat Rev Microbiol 17:233–245
Branche AR, Saiman L, Walsh EE et al (2022) Incidence of respiratory syncytial virus infection among hospitalized adults, 2017–2020. Clin Infect Dis 74:1004–1011
Chang J, Srikiatkhachorn A, Braciale TJ (2001) Visualization and characterization of respiratory Syncytial Virus F-Specific CD8 + T cells during experimental virus infection. J Immunol 167:4254–4260. https://doi.org/10.4049/jimmunol.167.8.4254
Chen J, Liu H, Yang J, Chou KC (2007) Prediction of linear B-cell epitopes using amino acid pair antigenicity scale. Amino Acids 33:423–428. https://doi.org/10.1007/s00726-006-0485-9
Chou K-C (1999) Using pair-coupled amino acid composition to predict protein secondary structure content. J Protein Chem 18:473–480
Collins PL, Melero JA (2011) Progress in understanding and controlling respiratory syncytial virus: still crazy after all these years. Virus Res 162:80–99. https://doi.org/10.1016/j.virusres.2011.09.020
Dhanda SK, Usmani SS, Agrawal P et al (2017) Novel in silico tools for designing peptide-based subunit vaccines and immunotherapeutics. Brief Bioinform 18:467–478
Dimitrov I, Flower DR, Doytchinova I (2013) AllerTOP-a server for in silico prediction of allergens. In: BMC bioinformatics. BioMed Central, pp 1–9
Dimitrov I, Bangov I, Flower DR, Doytchinova I (2014) AllerTOP v. 2—a server for in silico prediction of allergens. J Mol Model 20:1–6
Duquesnoy RJ, Marrari M, Marroquim MS et al (2019) Second update of the international registry of HLA epitopes. I. The HLA-ABC epitope database. Hum Immunol 80:103–106
EL-Manzalawy Y, Dobbs D, Honavar V (2008) Predicting linear B‐cell epitopes using string kernels. J Mol Recognit An Interdiscip J 21:243–255
Emini EA, Hughes JV, Perlow D, Boger J (1985) Induction of hepatitis a virus-neutralizing antibody by a virus-specific synthetic peptide. J Virol 55:836–839
Gilman MSA, Castellanos CA, Chen M et al (2017) Rapid profiling of RSV antibody repertoires from the memory B cells of naturally infected adult donors. 1:1–21. https://doi.org/10.1126/sciimmunol.aaj1879.Rapid
Graham BS (2011) Biological challenges and technological opportunities for respiratory syncytial virus vaccine development - Graham – 2010 - immunological reviews - Wiley Online Library. Immunol Rev 149–166
Hall CB (2001) Respiratory Syncytial Virus and Parainfluenza Virus. N Engl J Med 344:1917–1928. https://doi.org/10.1056/nejm200106213442507
Jiang L, Zhou J-M, Yin Y et al (2010) Selection and identification of B-cell epitope on NS1 protein of dengue virus type 2. Virus Res 150:49–55
Karplus PA, Schulz GE (1985) Prediction of chain flexibility in proteins. Naturwissenschaften 72:212–213
Khan MSA, Nain Z, Syed S, Bin et al (2021) Computational formulation and immune dynamics of a multi-peptide vaccine candidate against Crimean-Congo hemorrhagic fever virus. Mol Cell Probes 55:101693. https://doi.org/10.1016/j.mcp.2020.101693
Kolaskar AS, Tongaonkar PC (1990) A semi-empirical method for prediction of antigenic determinants on protein antigens. FEBS Lett 276:172–174
Larsen JEP, Lund O, Nielsen M (2006) Improved method for predicting linear B-cell epitopes. Immunome Res 2:1–7
Li Y, Wang X, Blau DM et al (2022) Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis. Lancet 399:2047–2064
Liu R, Hu J (2011) HemeBIND: a novel method for heme binding residue prediction by combining structural and sequence information. BMC Bioinformatics 12. https://doi.org/10.1186/1471-2105-12-207
McLaughlin JM, Khan F, Begier E et al (2022) Rates of medically attended RSV among US adults: a systematic review and meta-analysis. Open Forum Infectious Diseases. Oxford University Press, p ofac300
Mohan M, Shanmugaraja P, Krishnan R et al (2020) In silico prediction of b-cell epitopes of dengue virus – a reverse vaccinology approach. 10:77–85. https://doi.org/10.7324/JAPS.2020.10109
Morrison TG (1988) Structure, function, and intracellular processing of paramyxovirus membrane proteins. Virus Res 10:113–135. https://doi.org/10.1016/0168-1702(88)90010-X
Mousa JJ, Sauer MF, Sevy AM et al (2016) Structural basis for nonneutralizing antibody competition at antigenic site II of the respiratory syncytial virus fusion protein. Proc Natl Acad Sci 113:E6849–E6858. https://doi.org/10.1073/pnas.1609449113
Nair H, Nokes DJ, Gessner BD et al (2010) Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet 375:1545–1555
Odorico M, Pellequer J (2003) BEPITOPE: predicting the location of continuous epitopes and patterns in proteins. J Mol Recognit 16:20–22
Parker JMR, Guo D, Hodges RS (1986) New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: correlation of predicted surface residues with antigenicity and x-ray-derived accessible sites. Biochemistry 25:5425–5432
Ponomarenko JV, Bourne PE (2007) Antibody-protein interactions: benchmark datasets and prediction tools evaluation. BMC Struct Biol 7:1–19
Ponomarenko J, Bui HH, Li W et al (2008) ElliPro: a new structure-based tool for the prediction of antibody epitopes. BMC Bioinformatics 9:1–8. https://doi.org/10.1186/1471-2105-9-514
Purcell AW, McCluskey J, Rossjohn J (2007) More than one reason to rethink the use of peptides in vaccine design. Nat Rev Drug Discov 6:404–414. https://doi.org/10.1038/nrd2224
Saha S, Raghava GPS (2004) BcePred: prediction of continuous B-cell epitopes in antigenic sequences using physico-chemical properties. In: International Conference on Artificial Immune Systems. Springer, pp 197–204
Sayed S, Bin, Nain Z, Khan MSA et al (2020) Exploring Lassa Virus Proteome to Design a Multi-epitope Vaccine through Immunoinformatics and Immune Simulation analyses. Int J Pept Res Ther 26:2089–2107. https://doi.org/10.1007/s10989-019-10003-8
Schmidt ME, Meyerholz DK, Varga SM (2020) Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection. Mucosal Immunol 13:507–517. https://doi.org/10.1038/s41385-019-0243-4
Schrödinger L, DeLano W (2020) No Title. PyMOL Retrieved from http//www.pymol.org/pymol
Shinoff JJ, O’Brien KL, Thumar B et al (2008) Young Infants can develop protective levels of neutralizing antibody after infection with respiratory Syncytial Virus. J Infect Dis 198:1007–1015. https://doi.org/10.1086/591460
Skolnick J, Brylinski M (2009) FINDSITE: a combined evolution/structure-based approach to protein function prediction. Brief Bioinform 10:378–391. https://doi.org/10.1093/bib/bbp017
Stephens LM, Varga SM (2021) Considerations for a respiratory syncytial virus vaccine targeting an elderly population. Vaccines 9:624
Swedan S, Musiyenko A, Barik S (2009) Respiratory Syncytial Virus nonstructural proteins decrease levels of multiple members of the Cellular Interferon Pathways. J Virol 83:9682–9693. https://doi.org/10.1128/jvi.00715-09
Sweredoski MJ, Baldi P (2008) PEPITO: improved discontinuous B-cell epitope prediction using multiple distance thresholds and half sphere exposure. Bioinformatics 24:1459–1460. https://doi.org/10.1093/bioinformatics/btn199
Thomas A, Milon A, Brasseur R (2004) Proteins-structure function and bioinformatics
Tsui P, Tornetta MA, Ames RS et al (1996) Isolation of a neutralizing human RSV antibody from a dominant, non-neutralizing immune repertoire by epitope-blocked panning. J Immunol 157
Vashi Y, Jagrit V, Kumar S (2020) Infection, Genetics and Evolution understanding the B and T cell epitopes of spike protein of severe acute respiratory syndrome coronavirus-2 : a computational way to predict the immunogens. Infect Genet Evol 84:104382. https://doi.org/10.1016/j.meegid.2020.104382
Acknowledgements
The authors thank the Department of Nanoscience and Technology, Bharathiar University, Coimbatore, Tamilnadu India, for providing vital computational services and consistent command throughout the research work.
Funding
No funding was received to assist with the preparation of this manuscript.
Author information
Authors and Affiliations
Contributions
Paramasivam Premasudha: Supervision, Investigation, Methodology, Data curation, Review & Editing. Manikandan Mohan: Conceptualization, Methodology, Validation, Data curation. Yogesh B. Narkhede: Validation, Data curation, Review & Editing. Gayathri Anandhan: Methodology, Analysis, Data curation, Writing.
Corresponding authors
Ethics declarations
Competing interests
The authors declare no competing interests.
Ethical approval
This article contains no research involving human participants or animals that were conducted by any of the authors.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Anandhan, G., Narkhede, Y.B., Mohan, M. et al. In silico Approach for B Cell Epitopes Prediction of Respiratory Syncytial Virus. Int J Pept Res Ther 29, 75 (2023). https://doi.org/10.1007/s10989-023-10547-w
Accepted:
Published:
DOI: https://doi.org/10.1007/s10989-023-10547-w