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In this study, we used system\u2010level 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\u2010pathogen\u2010protein interactions, pathway studies, and <jats:italic>in silico<\/jats:italic> binding affinity analysis. <jats:italic>Results<\/jats:italic>. 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\u2010terminal with a 23.9\u2009kDa 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 (\u201012.49 and \u201010.48\u2009kcal\/mol for MHC classes I and II, respectively). This interaction showed that a polyvalent construct could manage and control this disease. <jats:italic>Conclusion<\/jats:italic>. Our vaccinomics and system\u2010level investigation could be appropriate to trigger the host immune system to prevent RSV infection.<\/jats:p>","DOI":"10.1155\/2021\/9940010","type":"journal-article","created":{"date-parts":[[2021,5,28]],"date-time":"2021-05-28T23:56:12Z","timestamp":1622246172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Designing of Potential Polyvalent Vaccine Model for Respiratory Syncytial Virus by System Level Immunoinformatics Approaches"],"prefix":"10.1155","volume":"2021","author":[{"given":"Syeda Tahira Qousain","family":"Naqvi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mamoona","family":"Yasmeen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehreen","family":"Ismail","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8068-4144","authenticated-orcid":false,"given":"Syed Aun","family":"Muhammad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed","family":"Nawazish-i-Husain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amjad","family":"Ali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fahad","family":"Munir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5463-6459","authenticated-orcid":false,"given":"QiYu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,28]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243283"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1053\/prrv.2000.0050"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00010-16"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00090-16"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2016.03.109"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.11.106"},{"key":"e_1_2_10_7_2","article-title":"Respiratory syncytial virus: current and emerging treatment options","volume":"6","author":"Turner T. 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