{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:20:45Z","timestamp":1777454445015,"version":"3.51.4"},"reference-count":87,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Bioinform Biol Insights"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:p>\n                    Cervical cancer remains a major global health burden, with high-risk human papillomavirus (HPV), particularly HPV-16, responsible for most cases. While licensed prophylactic HPV vaccines are effective, their type-restricted coverage and lack of therapeutic activity highlight the need for next-generation vaccine strategies. In this study, a systems vaccinology-based approach was used to design a multi-epitope vaccine with both prophylactic and therapeutic potential against HPV-16. Immunodominant epitopes eliciting immune responses from HPV-16 E5, E6, E7, and L2 proteins were identified using immunoinformatics methods. Transcriptomic and pathway enrichment analysis of cervical cancer data sets identified interleukin-17A (IL-17A) signaling as a favorable immune axis, supporting its inclusion as a cytokine adjuvant. Population coverage evaluation demonstrated broad global applicability, with a predicted coverage of 99.98% across MHC class I and II alleles. Among 7 designed constructs, 1 candidate (model D) exhibited favorable physicochemical and structural properties, including high predicted solubility (73%), strong model quality, and antigenic potential. Docking analyses indicated strong correlations between native complexes and the corresponding vaccine-IL-17 receptor A and C complexes (Pearson\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    \u2009=\u2009.98 and .88, respectively). Molecular dynamics simulations over 500 ns confirmed structural stability, with favorable MM\/PBSA binding free energies (\u0394G_total \u2248 \u221231 kJ\/mol). Immune response simulations demonstrated activation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T-cells, memory B-cell formation, and a predominantly IFN-\u03b3 immune response. These findings demonstrate that the proposed construct is a promising HPV-16 vaccine candidate; nevertheless, targeted in vitro and in vivo studies are essential to confirm its immunogenicity, efficacy, and safety prior to further clinical developments.\n                  <\/jats:p>","DOI":"10.1177\/11779322261437247","type":"journal-article","created":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T16:25:14Z","timestamp":1776615914000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Systems Vaccinology-Integrated Proteomics to Develop a Novel Prophylactic and Therapeutic Vaccine Against Human Papillomavirus 16"],"prefix":"10.1177","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-4944","authenticated-orcid":false,"given":"Shirin","family":"Fathi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran"},{"name":"Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aida","family":"Solhjoo","sequence":"additional","affiliation":[{"name":"Department of Quality Control of Drug Products, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashkan","family":"Bagheri","sequence":"additional","affiliation":[{"name":"Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amirhossein","family":"Sakhteman","sequence":"additional","affiliation":[{"name":"Department of Molecular Life Sciences, School of Life Sciences, Technical University of Munich, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Younes","family":"Ghasemi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran"},{"name":"Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manica","family":"Negahdaripour","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran"},{"name":"Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, 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