{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:56:52Z","timestamp":1791921412597,"version":"4.3.4"},"reference-count":135,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of the Ryukyus"},{"name":"Support Program for Frontier Scientific Research from the Faculty of Medicine, University of the Ryukyus"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Spike protein sequences in SARS-CoV-2 have been employed for vaccine epitopes, but many short constituent sequences (SCSs) in the spike protein are present in the human proteome, suggesting that some anti-spike antibodies induced by infection or vaccination may be autoantibodies against human proteins. To evaluate this possibility of \u201cmolecular mimicry\u201d in silico and in vitro, we exhaustively identified common SCSs (cSCSs) found both in spike and human proteins bioinformatically. The commonality of SCSs between the two systems seemed to be coincidental, and only some cSCSs were likely to be relevant to potential self-epitopes based on three-dimensional information. Among three antibodies raised against cSCS-containing spike peptides, only the antibody against EPLDVL showed high affinity for the spike protein and reacted with an EPLDVL-containing peptide from the human unc-80 homolog protein. Western blot analysis revealed that this antibody also reacted with several human proteins expressed mainly in the small intestine, ovary, and stomach. Taken together, these results showed that most cSCSs are likely incapable of inducing autoantibodies but that at least EPLDVL functions as a self-epitope, suggesting a serious possibility of infection-induced or vaccine-induced autoantibodies in humans. High-risk cSCSs, including EPLDVL, should be excluded from vaccine epitopes to prevent potential autoimmune disorders.<\/jats:p>","DOI":"10.3390\/vaccines12050539","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:59:37Z","timestamp":1715677177000},"page":"539","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["In Silico and In Vitro Evaluation of the Molecular Mimicry of the SARS-CoV-2 Spike Protein by Common Short Constituent Sequences (cSCSs) in the Human Proteome: Toward Safer Epitope Design for Vaccine Development"],"prefix":"10.3390","volume":"12","author":[{"given":"Yuya","family":"Mizuno","sequence":"first","affiliation":[{"name":"The BCPH Unit of Molecular Physiology, Department of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, Senbaru, Nishihara 903-0213, Okinawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Nakasone","sequence":"additional","affiliation":[{"name":"Computer Science and Intelligent Systems Unit, Department of Engineering, Faculty of Engineering, University of the Ryukyus, Senbaru, Nishihara 903-0213, Okinawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1583-2523","authenticated-orcid":false,"given":"Morikazu","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Computer Science and Intelligent Systems Unit, Department of Engineering, Faculty of Engineering, University of the Ryukyus, Senbaru, Nishihara 903-0213, Okinawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3425-7085","authenticated-orcid":false,"given":"Joji M.","family":"Otaki","sequence":"additional","affiliation":[{"name":"The BCPH Unit of Molecular Physiology, Department of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, Senbaru, Nishihara 903-0213, Okinawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"658519","DOI":"10.3389\/fimmu.2021.658519","article-title":"Potential therapeutic targets and vaccine development for SARS-CoV-2\/COVID-19 pandemic management: A review on the recent update","volume":"12","author":"Anand","year":"2021","journal-title":"Front. 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