{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:12:07Z","timestamp":1792725127650,"version":"4.5.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070920"],"award-info":[{"award-number":["32070920"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004829","name":"Department of Science and Technology of Sichuan Province","doi-asserted-by":"publisher","award":["2019YFN0134"],"award-info":[{"award-number":["2019YFN0134"]}],"id":[{"id":"10.13039\/501100004829","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2682020ZT87"],"award-info":[{"award-number":["2682020ZT87"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Microb Cell Fact"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>The global pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the need to develop safe and effective vaccines with a top priority. Multiple vaccine candidates are under development, and several vaccines are currently available. Efforts need to be undertaken to counter the threat of the global COVID-19 pandemic.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We generated a <jats:italic>Saccharomyces cerevisiae<\/jats:italic> (<jats:italic>S. cerevisiae<\/jats:italic>)-based SARS-CoV-2 vaccine, EBY100\/pYD1-RBD, in which the full-length receptor binding domain (RBD) of the spike protein of SARS-CoV-2 was expressed on the surface of yeast. Mice vaccinated orally with unadjuvanted EBY100\/pYD1-RBD could produce significant humoral and mucosal responses as well as robust cellular immune responses. Notably, EBY100\/pYD1-RBD elicited a mixed Th1\/Th2-type cellular immune response with a Th1-biased immune response in a mouse model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings highlight the importance of the RBD as a key target to design and develop vaccines against SARS-CoV-2 and provide evidence of oral administration of a <jats:italic>S. cerevisiae<\/jats:italic>-based SARS-CoV-2 vaccine eliciting significant immune responses. Most importantly, the <jats:italic>S. cerevisiae<\/jats:italic> surface display system can serve as a universal technology platform and be applied to develop other oral viral or bacterial vaccines.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12934-021-01584-5","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T09:05:37Z","timestamp":1620205537000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Immune response induced by oral administration with a Saccharomyces cerevisiae-based SARS-CoV-2 vaccine in mice"],"prefix":"10.1186","volume":"20","author":[{"given":"Tong","family":"Gao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangqin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5156-4258","authenticated-orcid":false,"given":"Han","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,5,5]]},"reference":[{"key":"1584_CR1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41577-020-00480-0","volume":"21","author":"L Dai","year":"2021","unstructured":"Dai L, Gao GF. Viral targets for vaccines against COVID-19. Nat Rev Immunol. 2021;21:73\u2013182.","journal-title":"Nat Rev Immunol"},{"key":"1584_CR2","unstructured":"https:\/\/covid19.who.int\/."},{"key":"1584_CR3","unstructured":"https:\/\/www.who.int\/emergencies\/diseases\/novel-coronavirus-2019\/situation-reports."},{"key":"1584_CR4","doi-asserted-by":"publisher","first-page":"m4857","DOI":"10.1136\/bmj.m4857","volume":"371","author":"J Wise","year":"2020","unstructured":"Wise J. Covid-19: New coronavirus variant is identified in UK. BMJ. 2020;371:m4857.","journal-title":"BMJ"},{"key":"1584_CR5","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1002\/jmv.25681","volume":"92","author":"Y Chen","year":"2020","unstructured":"Chen Y, Liu Q, Guo D. Emerging coronaviruses: genome structure, replication, and pathogenesis. J Med Virol. 2020;92:418\u201323.","journal-title":"J Med Virol"},{"key":"1584_CR6","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/s41586-020-2286-9","volume":"583","author":"DE Gordon","year":"2020","unstructured":"Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583:459\u201368.","journal-title":"Nature"},{"key":"1584_CR7","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.jpha.2020.03.001","volume":"10","author":"X Li","year":"2020","unstructured":"Li X, Geng M, Peng Y, Meng L, Lu S. Molecular immune pathogenesis and diagnosis of COVID-19. J Pharm Anal. 2020;10:102\u20138.","journal-title":"J Pharm Anal"},{"key":"1584_CR8","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","volume":"181","author":"M Hoffmann","year":"2020","unstructured":"Hoffmann M, Kleine-Weber H, Schroeder S, Kr\u00fcger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271-80.e8.","journal-title":"Cell"},{"key":"1584_CR9","doi-asserted-by":"publisher","first-page":"1444","DOI":"10.1126\/science.abb2762","volume":"367","author":"R Yan","year":"2020","unstructured":"Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science. 2020;367:1444\u20138.","journal-title":"Science"},{"key":"1584_CR10","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s41586-020-2599-8","volume":"586","author":"J Yang","year":"2020","unstructured":"Yang J, Wang W, Chen Z, Lu S, Yang F, Bi Z, et al. A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity. Nature. 2020;586:572\u20137.","journal-title":"Nature"},{"key":"1584_CR11","doi-asserted-by":"publisher","first-page":"1735","DOI":"10.1016\/j.cell.2020.11.032","volume":"183","author":"AC Walls","year":"2020","unstructured":"Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell. 2020;183:1735.","journal-title":"Cell"},{"key":"1584_CR12","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","volume":"19","author":"B Hu","year":"2021","unstructured":"Hu B, Guo H, Zhou P, Shi ZL. Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol. 2021;19:141\u201354.","journal-title":"Nat Rev Microbiol"},{"key":"1584_CR13","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/s41564-020-0688-y","volume":"5","author":"M Letko","year":"2020","unstructured":"Letko M, Marzi A, Munster V. Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol. 2020;5:562\u20139.","journal-title":"Nat Microbiol"},{"key":"1584_CR14","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","volume":"579","author":"P Zhou","year":"2020","unstructured":"Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579:270\u20133.","journal-title":"Nature"},{"key":"1584_CR15","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1126\/science.abb8923","volume":"368","author":"BS Graham","year":"2020","unstructured":"Graham BS. Rapid COVID-19 vaccine development. Science. 2020;368:945\u20136.","journal-title":"Science"},{"key":"1584_CR16","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1126\/science.abc1932","volume":"369","author":"Q Gao","year":"2020","unstructured":"Gao Q, Bao L, Mao H, Wang L, Xu K, Yang M, et al. Development of an inactivated vaccine candidate for SARS-CoV-2. Science. 2020;369:77\u201381.","journal-title":"Science"},{"key":"1584_CR17","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/S0140-6736(20)31605-6","volume":"396","author":"FC Zhu","year":"2020","unstructured":"Zhu FC, Guan XH, Li YH, Huang JY, Jiang T, Hou LH, et al. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2020;396:479\u201388.","journal-title":"Lancet"},{"key":"1584_CR18","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/S0140-6736(20)31604-4","volume":"396","author":"PM Folegatti","year":"2020","unstructured":"Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1\/2, single-blind, randomised controlled trial. Lancet. 2020;396:467\u201378.","journal-title":"Lancet"},{"key":"1584_CR19","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/S0140-6736(20)31866-3","volume":"396","author":"DY Logunov","year":"2020","unstructured":"Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatulin AI, Shcheblyakov DV, Dzharullaeva AS, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase 1\/2 studies from Russi. Lancet. 2020;396:887\u201397.","journal-title":"Lancet"},{"key":"1584_CR20","doi-asserted-by":"publisher","first-page":"2601","DOI":"10.1038\/s41467-020-16505-0","volume":"11","author":"TRF Smith","year":"2020","unstructured":"Smith TRF, Patel A, Ramos S, Elwood D, Zhu X, Yan J, et al. Immunogenicity of a DNA vaccine candidate for COVID-19. Nat Commun. 2020;11:2601.","journal-title":"Nat Commun"},{"key":"1584_CR21","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/s41586-020-2622-0","volume":"586","author":"KS Corbett","year":"2020","unstructured":"Corbett KS, Edwards DK, Leist SR, Abiona OM, Boyoglu-Barnum S, Gillespie RA, et al. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature. 2020;586:567\u201371.","journal-title":"Nature"},{"key":"1584_CR22","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1056\/NEJMoa2022483","volume":"383","author":"LA Jackson","year":"2020","unstructured":"Jackson LA, Anderson EJ, Rouphael NG, Roberts PC, Makhene M, Coler RN, et al. An mRNA vaccine against SARS-CoV-2-preliminary report. N Engl J Med. 2020;383:1920\u201331.","journal-title":"N Engl J Med"},{"key":"1584_CR23","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1016\/j.cell.2020.06.035","volume":"182","author":"L Dai","year":"2020","unstructured":"Dai L, Zheng T, Xu K, Han Y, Xu L, Huang E, et al. A universal design of betacoronavirus vaccines against COVID-19, MERS, and SARS. Cell. 2020;182:722\u201333.","journal-title":"Cell"},{"key":"1584_CR24","first-page":"foz007","volume":"19","author":"R Kumar","year":"2019","unstructured":"Kumar R, Kumar P. Yeast-based vaccines: New perspective in vaccine development and application. FEMS Yeast Res. 2019;19:foz007.","journal-title":"FEMS Yeast Res"},{"key":"1584_CR25","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s12934-020-01316-1","volume":"19","author":"H Lei","year":"2020","unstructured":"Lei H, Xie B, Gao T, Cen Q, Ren Y. Yeast display platform technology to prepare oral vaccine against lethal H7N9 virus challenge in mice. Microb Cell Fact. 2020;19:53.","journal-title":"Microb Cell Fact"},{"key":"1584_CR26","doi-asserted-by":"publisher","first-page":"e12772","DOI":"10.1111\/hel.12772","volume":"26","author":"Q Cen","year":"2021","unstructured":"Cen Q, Gao T, Ren Y, Lu X, Lei H. Immune evaluation of a Saccharomyces cerevisiae-based oral vaccine against Helicobacter pylori in mice. Helicobacter. 2021;26:e12772.","journal-title":"Helicobacter"},{"key":"1584_CR27","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/978-1-4939-3389-1_32","volume":"1404","author":"S Shibasaki","year":"2016","unstructured":"Shibasaki S, Ueda M. Oral Vaccine Development by Molecular Display Methods Using Microbial Cells. Methods Mol Biol. 2016;1404:497\u2013509.","journal-title":"Methods Mol Biol"},{"key":"1584_CR28","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.immuni.2020.03.007","volume":"52","author":"F Amanat","year":"2020","unstructured":"Amanat F, Krammer F. SARS-CoV-2 vaccines: status report. Immunity. 2020;52:583\u20139.","journal-title":"Immunity"},{"key":"1584_CR29","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1126\/science.abc5312","volume":"368","author":"L Corey","year":"2020","unstructured":"Corey L, Mascola JR, Fauci AS, Collins FS. A strategic approach to COVID-19 vaccine R&D. Science. 2020;368:948\u201350.","journal-title":"Science"},{"key":"1584_CR30","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1080\/22221751.2020.1743767","volume":"9","author":"J Nie","year":"2020","unstructured":"Nie J, Li Q, Wu J, Zhao C, Hao H, Liu H, et al. Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2. Emerg Microbes Infect. 2020;9:680\u20136.","journal-title":"Emerg Microbes Infect"}],"container-title":["Microbial Cell Factories"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12934-021-01584-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12934-021-01584-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12934-021-01584-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T09:17:56Z","timestamp":1620206276000},"score":1,"resource":{"primary":{"URL":"https:\/\/microbialcellfactories.biomedcentral.com\/articles\/10.1186\/s12934-021-01584-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,5]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["1584"],"URL":"https:\/\/doi.org\/10.1186\/s12934-021-01584-5","relation":{},"ISSN":["1475-2859"],"issn-type":[{"value":"1475-2859","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,5]]},"assertion":[{"value":"29 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All animal studies complied with the Guidelines for the Use and Care of Experimental Animals and were approved by the Animal Committee of the Institute of Southwest Jiaotong University.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"All authors declare no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"95"}}