{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:58:39Z","timestamp":1773820719201,"version":"3.50.1"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioinform."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Recurrent zoonotic spillovers and continuous antigenic evolution among betacoronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2, highlight the urgent need for a broad-spectrum vaccine capable of eliciting cross-protective immunity. Conventional vaccines, although effective against specific strains, may be limited by antigenic mismatch and waning immunity. This study aimed to design a multi-epitope pan-betacoronavirus vaccine targeting conserved regions within the receptor-binding domain (RBD) using an integrated immunoinformatics and reverse vaccinology framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and linear B-cell epitopes were predicted and screened for antigenicity, allergenicity, toxicity, and non-homology to host proteins. Selected epitopes were assembled into a 285\u2013amino acid multi-epitope construct using optimized linkers (AAY, GPGPG, EAAAK, and GGGGS) and human \u03b2-defensin 3 as an adjuvant. Structural modeling and refinement were performed to generate a three-dimensional vaccine model, followed by molecular docking with a B-cell receptor (BCR) Fab model using ClusPro. Molecular dynamics simulations were conducted to evaluate structural stability, and immune responses were assessed through computational immune simulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The refined vaccine construct produced a stable structural model with a C-score of \u22123.60. Molecular docking identified a highly ranked complex from a well-populated cluster (Cluster 1; 49 members) with a Lowest Energy score of \u2212865.9, indicating favorable interface complementarity under the docking scoring function. Molecular dynamics simulation over 100 ns supported the structural integrity and dynamic stability of the complex, with minimal backbone deviation and sustained intermolecular interactions. Immune simulations predicted coordinated humoral and cellular responses following a simulated prime\u2013boost regimen, including increased antibody titers, elevated IL-2 and IFN-\u03b3 levels, and sustained memory B- and T-cell populations. The selected epitope set showed an estimated global HLA population coverage of 93.28%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study identifies a promising\n                      <jats:italic>in silico<\/jats:italic>\n                      multi-epitope RBD-based pan-betacoronavirus vaccine candidate with predicted broad HLA population coverage and favorable structural stability. These findings provide a computational basis for subsequent experimental validation of the construct\u2019s immunogenicity, safety, and potential cross-protective capacity in relevant\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      models.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fbinf.2026.1784011","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:58:00Z","timestamp":1773817080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A multi-epitope pan-betacoronavirus vaccine construct predicted to induce broad-spectrum and durable immune responses: an immunoinformatics approach"],"prefix":"10.3389","volume":"6","author":[{"given":"Anabella Margareth","family":"Arapa","sequence":"first","affiliation":[{"name":"Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University","place":["Manado, North Sulawesi, Indonesia"]}]},{"given":"Trina Ekawati","family":"Tallei","sequence":"additional","affiliation":[{"name":"Department of Biology, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University","place":["Manado, North Sulawesi, Indonesia"]},{"name":"Department of Biology, Faculty of Medicine, Sam Ratulangi University","place":["Manado, North Sulawesi, Indonesia"]},{"name":"Department of Pathology, College of Korean Medicine, Kyung Hee University","place":["Seoul, Republic of Korea"]}]},{"given":"Rinaldi","family":"Idroes","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Mathematics and Natural Sciences, Universitas Syiah Kuala","place":["Banda Aceh, Indonesia"]}]},{"family":"Fatimawali","sequence":"additional","affiliation":[{"name":"Pharmacy Study Program, Faculty of Mathematics and Natural Sciences, Sam Ratulangi 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