{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:11:33Z","timestamp":1790395893187,"version":"4.1.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T00:00:00Z","timestamp":1594425600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T00:00:00Z","timestamp":1594425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31770998"],"award-info":[{"award-number":["31770998"]}],"id":[{"id":"10.13039\/501100001809","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":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Zoonotic hepatitis E virus (HEV) infection emerged as a serious threat in the industrialized countries. The aim of this study is exploring a new approach for the control of zoonotic HEV in its main host (swine) through the design and development of an economically interesting chimeric vaccine against HEV and against a devastating swine infection: the foot-and-mouth disease virus (FMDV) infection.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>First, we adopted a computational approach for rational and effective screening of the different HEV-FMDV chimeric proteins. Next, we further expressed and purified the selected chimeric immunogens in <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>E. coli<\/jats:italic>) using molecular cloning techniques. Finally, we assessed the antigenicity and immunogenicity profiles of the chimeric vaccine candidates. Following this methodology, we designed and successfully produced an HEV-FMDV chimeric vaccine candidate (Seq\u00a08-P222) that was highly over-expressed in <jats:italic>E. coli<\/jats:italic> as a soluble protein and could self-assemble into virus-like particles. Moreover, the vaccine candidate was thermo-stable and exhibited optimal antigenicity and immunogenicity properties.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This study provides new insights into the vaccine development technology by using bioinformatics for the selection of the best candidates from larger sets prior to experimentation. It also presents the first HEV-FMDV chimeric protein produced in <jats:italic>E. coli<\/jats:italic> as a promising chimeric vaccine candidate that could participate in reducing the transmission of zoonotic HEV to humans while preventing the highly contagious foot-and-mouth disease in swine.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12934-020-01394-1","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T05:02:48Z","timestamp":1594443768000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Design and development of a chimeric vaccine candidate against zoonotic hepatitis E and foot-and-mouth disease"],"prefix":"10.1186","volume":"19","author":[{"given":"Nouredine","family":"Behloul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarra","family":"Baha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenzhen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuliang","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruihua","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,11]]},"reference":[{"key":"1394_CR1","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1056\/NEJMra1204512","volume":"367","author":"JH Hoofnagle","year":"2012","unstructured":"Hoofnagle JH, Nelson KE, Purcell RH. Hepatitis E. N Engl J Med. 2012;367:1237\u201344.","journal-title":"N Engl J Med"},{"key":"1394_CR2","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.1016\/S0140-6736(11)61849-7","volume":"379","author":"N Kamar","year":"2012","unstructured":"Kamar N, Bendall R, Legrand-Abravanel F, Xia NS, Ijaz S, Izopet J, Dalton HR. Hepatitis E. Lancet. 2012;379:2477\u201388.","journal-title":"Lancet"},{"key":"1394_CR3","doi-asserted-by":"publisher","first-page":"2396","DOI":"10.3389\/fmicb.2017.02396","volume":"8","author":"Y Nan","year":"2017","unstructured":"Nan Y, Wu C, Zhao Q, Zhou EM. Zoonotic Hepatitis E virus: an ignored risk for public health. Front Microbiol. 2017;8:2396.","journal-title":"Front Microbiol"},{"key":"1394_CR4","doi-asserted-by":"publisher","first-page":"17086","DOI":"10.1038\/nrdp.2017.86","volume":"3","author":"N Kamar","year":"2017","unstructured":"Kamar N, Izopet J, Pavio N, Aggarwal R, Labrique A, Wedemeyer H, Dalton HR. Hepatitis E virus infection. Nat Rev Dis Primers. 2017;3:17086.","journal-title":"Nat Rev Dis Primers"},{"key":"1394_CR5","doi-asserted-by":"publisher","first-page":"270","DOI":"10.3390\/v8100270","volume":"8","author":"V Doceul","year":"2016","unstructured":"Doceul V, Bagdassarian E, Demange A, Pavio N. Zoonotic Hepatitis E virus: classification, animal reservoirs and transmission routes. Viruses. 2016;8:270.","journal-title":"Viruses"},{"key":"1394_CR6","doi-asserted-by":"publisher","first-page":"7030","DOI":"10.3748\/wjg.v22.i31.7030","volume":"22","author":"MS Khuroo","year":"2016","unstructured":"Khuroo MS, Khuroo MS, Khuroo NS. Hepatitis E: discovery, global impact, control and cure. World J Gastroenterol. 2016;22:7030\u201345.","journal-title":"World J Gastroenterol"},{"key":"1394_CR7","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1056\/NEJMoa1406011","volume":"372","author":"J Zhang","year":"2015","unstructured":"Zhang J, Zhang XF, Huang SJ, Wu T, Hu YM, Wang ZZ, Wang H, Jiang HM, Wang YJ, Yan Q, et al. Long-term efficacy of a hepatitis E vaccine. N Engl J Med. 2015;372:914\u201322.","journal-title":"N Engl J Med"},{"key":"1394_CR8","doi-asserted-by":"publisher","first-page":"5073","DOI":"10.1016\/j.vaccine.2017.05.072","volume":"35","author":"YF Cao","year":"2017","unstructured":"Cao YF, Tao H, Hu YM, Shi CB, Wu X, Liang Q, Chi CP, Li L, Liang ZL, Meng JH, et al. A phase 1 randomized open-label clinical study to evaluate the safety and tolerability of a novel recombinant hepatitis E vaccine. Vaccine. 2017;35:5073\u201380.","journal-title":"Vaccine"},{"key":"1394_CR9","unstructured":"World Health Organization. Hepatitis E position paper. https:\/\/www.who.int\/immunization\/policy\/position_papers\/hepatitis_e\/en\/."},{"key":"1394_CR10","doi-asserted-by":"publisher","first-page":"17091","DOI":"10.1038\/nrdp.2017.91","volume":"3","author":"AR Fooks","year":"2017","unstructured":"Fooks AR, Cliquet F, Finke S, Freuling C, Hemachudha T, Mani RS, Muller T, Nadin-Davis S, Picard-Meyer E, Wilde H, Banyard AC. Rabies. Nat Rev Dis Primers. 2017;3:17091.","journal-title":"Nat Rev Dis Primers"},{"key":"1394_CR11","unstructured":"World Organization for Animal Health: Foot and Mouth Disease (FMD). http:\/\/www.oie.int\/animal-health-in-the-world\/official-disease-status\/fmd\/technical-disease-cards\/."},{"key":"1394_CR12","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1038\/s41598-018-20137-2","volume":"8","author":"W Wei","year":"2018","unstructured":"Wei W, Behloul N, Baha S, Liu Z, Aslam MS, Meng J. Dimerization: a structural feature for the protection of hepatitis E virus capsid protein against trypsinization. Sci Rep. 2018;8:1738.","journal-title":"Sci Rep"},{"key":"1394_CR13","doi-asserted-by":"publisher","first-page":"19910","DOI":"10.1074\/jbc.M115.649764","volume":"290","author":"M Zhao","year":"2015","unstructured":"Zhao M, Li XJ, Tang ZM, Yang F, Wang SL, Cai W, Zhang K, Xia NS, Zheng ZZ. A comprehensive study of neutralizing antigenic sites on the hepatitis E virus (HEV) capsid by constructing, clustering, and characterizing a tool box. J Biol Chem. 2015;290:19910\u201322.","journal-title":"J Biol Chem"},{"key":"1394_CR14","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1038\/cr.2015.34","volume":"25","author":"Y Gu","year":"2015","unstructured":"Gu Y, Tang X, Zhang X, Song C, Zheng M, Wang K, Zhang J, Ng MH, Hew CL, Li S, et al. Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody. Cell Res. 2015;25:604\u201320.","journal-title":"Cell Res"},{"key":"1394_CR15","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1002\/rmv.1719","volume":"22","author":"J Zhang","year":"2012","unstructured":"Zhang J, Li SW, Wu T, Zhao Q, Ng MH, Xia NS. Hepatitis E virus: neutralizing sites, diagnosis, and protective immunity. Rev Med Virol. 2012;22:339\u201349.","journal-title":"Rev Med Virol"},{"key":"1394_CR16","doi-asserted-by":"publisher","first-page":"10266","DOI":"10.1073\/pnas.1101309108","volume":"108","author":"X Tang","year":"2011","unstructured":"Tang X, Yang C, Gu Y, Song C, Zhang X, Wang Y, Zhang J, Hew CL, Li S, Xia N, Sivaraman J. Structural basis for the neutralization and genotype specificity of hepatitis E virus. Proc Natl Acad Sci USA. 2011;108:10266\u201371.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1394_CR17","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1006\/viro.2001.1093","volume":"288","author":"J Meng","year":"2001","unstructured":"Meng J, Dai X, Chang JC, Lopareva E, Pillot J, Fields HA, Khudyakov YE. Identification and characterization of the neutralization epitope(s) of the hepatitis E virus. Virology. 2001;288:203\u201311.","journal-title":"Virology"},{"key":"1394_CR18","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1093\/bioinformatics\/btu769","volume":"31","author":"I Samish","year":"2015","unstructured":"Samish I, Bourne PE, Najmanovich RJ. Achievements and challenges in structural bioinformatics and computational biophysics. Bioinformatics. 2015;31:146\u201350.","journal-title":"Bioinformatics"},{"key":"1394_CR19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/978-94-017-9245-5_1","volume":"827","author":"Q Xu","year":"2015","unstructured":"Xu Q, Dai H, Zhao T, Wei D. Introduction to structural bioinformatics. Adv Exp Med Biol. 2015;827:1\u20137.","journal-title":"Adv Exp Med Biol"},{"key":"1394_CR20","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1038\/nprot.2015.053","volume":"10","author":"LA Kelley","year":"2015","unstructured":"Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ. The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015;10:845\u201358.","journal-title":"Nat Protoc"},{"key":"1394_CR21","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.compbiolchem.2014.10.001","volume":"53","author":"M Dorn","year":"2014","unstructured":"Dorn M, Buriol LS, Lamb LC. Three-dimensional protein structure prediction: methods and computational strategies. Comput Biol Chem. 2014;53:251\u201376.","journal-title":"Comput Biol Chem"},{"key":"1394_CR22","doi-asserted-by":"publisher","first-page":"12992","DOI":"10.1073\/pnas.0904848106","volume":"106","author":"TS Guu","year":"2009","unstructured":"Guu TS, Liu Z, Ye Q, Mata DA, Li K, Yin C, Zhang J, Tao YJ. Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding. Proc Natl Acad Sci USA. 2009;106:12992\u20137.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1394_CR23","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1006\/biol.2001.0302","volume":"29","author":"CY Wang","year":"2001","unstructured":"Wang CY, Chang TY, Walfield AM, Ye J, Shen M, Zhang ML, Lubroth J, Chen SP, Li MC, Lin YL, et al. Synthetic peptide-based vaccine and diagnostic system for effective control of FMD. Biologicals. 2001;29:221\u20138.","journal-title":"Biologicals"},{"key":"1394_CR24","doi-asserted-by":"publisher","first-page":"12545","DOI":"10.1073\/pnas.94.23.12545","volume":"94","author":"JP Briand","year":"1997","unstructured":"Briand JP, Benkirane N, Guichard G, Newman JF, Van Regenmortel MH, Brown F, Muller S. A retro-inverso peptide corresponding to the GH loop of foot-and-mouth disease virus elicits high levels of long-lasting protective neutralizing antibodies. Proc Natl Acad Sci USA. 1997;94:12545\u201350.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1394_CR25","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1002\/j.1460-2075.1995.tb07158.x","volume":"14","author":"N Verdaguer","year":"1995","unstructured":"Verdaguer N, Mateu MG, Andreu D, Giralt E, Domingo E, Fita I. Structure of the major antigenic loop of foot-and-mouth disease virus complexed with a neutralizing antibody: direct involvement of the Arg-Gly-Asp motif in the interaction. EMBO J. 1995;14:1690\u20136.","journal-title":"EMBO J"},{"key":"1394_CR26","doi-asserted-by":"publisher","first-page":"12986","DOI":"10.1073\/pnas.0903699106","volume":"106","author":"T Yamashita","year":"2009","unstructured":"Yamashita T, Mori Y, Miyazaki N, Cheng RH, Yoshimura M, Unno H, Shima R, Moriishi K, Tsukihara T, Li TC, et al. Biological and immunological characteristics of hepatitis E virus-like particles based on the crystal structure. Proc Natl Acad Sci USA. 2009;106:12986\u201391.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1394_CR27","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1186\/s12934-017-0812-8","volume":"16","author":"N Behloul","year":"2017","unstructured":"Behloul N, Wei W, Baha S, Liu Z, Wen J, Meng J. Effects of mRNA secondary structure on the expression of HEV ORF2 proteins in Escherichia coli. Microb Cell Fact. 2017;16:200.","journal-title":"Microb Cell Fact"},{"key":"1394_CR28","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1126\/science.1241934","volume":"342","author":"DB Goodman","year":"2013","unstructured":"Goodman DB, Church GM, Kosuri S. Causes and effects of N-terminal codon bias in bacterial genes. Science. 2013;342:475\u20139.","journal-title":"Science"},{"key":"1394_CR29","doi-asserted-by":"publisher","first-page":"e1000537","DOI":"10.1371\/journal.ppat.1000537","volume":"5","author":"S Li","year":"2009","unstructured":"Li S, Tang X, Seetharaman J, Yang C, Gu Y, Zhang J, Du H, Shih JW, Hew CL, Sivaraman J, Xia N. Dimerization of hepatitis E virus capsid protein E2s domain is essential for virus-host interaction. PLoS Pathog. 2009;5:e1000537.","journal-title":"PLoS Pathog"},{"key":"1394_CR30","doi-asserted-by":"publisher","first-page":"3157","DOI":"10.1016\/j.vaccine.2004.12.020","volume":"23","author":"YH Zhou","year":"2005","unstructured":"Zhou YH, Purcell RH, Emerson SU. A truncated ORF2 protein contains the most immunogenic site on ORF2: antibody responses to non-vaccine sequences following challenge of vaccinated and non-vaccinated macaques with hepatitis E virus. Vaccine. 2005;23:3157\u201365.","journal-title":"Vaccine"},{"key":"1394_CR31","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s12896-016-0285-6","volume":"16","author":"Y Xiao","year":"2016","unstructured":"Xiao Y, Chen HY, Wang Y, Yin B, Lv C, Mo X, Yan H, Xuan Y, Huang Y, Pang W, et al. Large-scale production of foot-and-mouth disease virus (serotype Asia1) VLP vaccine in Escherichia coli and protection potency evaluation in cattle. BMC Biotechnol. 2016;16:56.","journal-title":"BMC Biotechnol"},{"key":"1394_CR32","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.vetmic.2013.11.023","volume":"168","author":"Y Cao","year":"2014","unstructured":"Cao Y, Lu Z, Li D, Fan P, Sun P, Bao H, Fu Y, Li P, Bai X, Chen Y, et al. Evaluation of cross-protection against three topotypes of serotype O foot-and-mouth disease virus in pigs vaccinated with multi-epitope protein vaccine incorporated with poly(I:C). Vet Microbiol. 2014;168:294\u2013301.","journal-title":"Vet Microbiol"},{"key":"1394_CR33","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.antiviral.2012.11.009","volume":"97","author":"Y Cao","year":"2013","unstructured":"Cao Y, Lu Z, Li Y, Sun P, Li D, Li P, Bai X, Fu Y, Bao H, Zhou C, et al. Poly(I:C) combined with multi-epitope protein vaccine completely protects against virulent foot-and-mouth disease virus challenge in pigs. Antiviral Res. 2013;97:145\u201353.","journal-title":"Antiviral Res"},{"key":"1394_CR34","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.coviro.2016.03.001","volume":"18","author":"KM Frietze","year":"2016","unstructured":"Frietze KM, Peabody DS, Chackerian B. Engineering virus-like particles as vaccine platforms. Curr Opin Virol. 2016;18:44\u20139.","journal-title":"Curr Opin Virol"},{"key":"1394_CR35","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/j.copbio.2013.02.008","volume":"24","author":"WA Rodriguez-Limas","year":"2013","unstructured":"Rodriguez-Limas WA, Sekar K, Tyo KE. Virus-like particles: the future of microbial factories and cell-free systems as platforms for vaccine development. Curr Opin Biotechnol. 2013;24:1089\u201393.","journal-title":"Curr Opin Biotechnol"},{"key":"1394_CR36","doi-asserted-by":"publisher","first-page":"e56417","DOI":"10.1371\/journal.pone.0056417","volume":"8","author":"E Fernandez","year":"2013","unstructured":"Fernandez E, Toledo JR, Mendez L, Gonzalez N, Parra F, Martin-Alonso JM, Limonta M, Sanchez K, Cabrales A, Estrada MP, et al. Conformational and thermal stability improvements for the large-scale production of yeast-derived rabbit hemorrhagic disease virus-like particles as multipurpose vaccine. PLoS ONE. 2013;8:e56417.","journal-title":"PLoS ONE"},{"key":"1394_CR37","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1002\/jps.22367","volume":"100","author":"AK Andrianov","year":"2011","unstructured":"Andrianov AK, Decollibus DP, Marin A, Webb A, Griffin Y, Webby RJ. PCPP-formulated H5N1 influenza vaccine displays improved stability and dose-sparing effect in lethal challenge studies. J Pharm Sci. 2011;100:1436\u201343.","journal-title":"J Pharm Sci"},{"key":"1394_CR38","doi-asserted-by":"publisher","first-page":"2606","DOI":"10.1128\/jvi.71.4.2606-2614.1997","volume":"71","author":"O Taboga","year":"1997","unstructured":"Taboga O, Tami C, Carrillo E, Nunez JI, Rodriguez A, Saiz JC, Blanco E, Valero ML, Roig X, Camarero JA, et al. A large-scale evaluation of peptide vaccines against foot-and-mouth disease: lack of solid protection in cattle and isolation of escape mutants. J Virol. 1997;71:2606\u201314.","journal-title":"J Virol"},{"key":"1394_CR39","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.antiviral.2016.03.005","volume":"129","author":"E Blanco","year":"2016","unstructured":"Blanco E, Guerra B, de la Torre BG, Defaus S, Dekker A, Andreu D, Sobrino F. Full protection of swine against foot-and-mouth disease by a bivalent B-cell epitope dendrimer peptide. Antiviral Res. 2016;129:74\u201380.","journal-title":"Antiviral Res"},{"key":"1394_CR40","doi-asserted-by":"publisher","first-page":"5772","DOI":"10.1016\/j.vaccine.2015.09.055","volume":"33","author":"H Zheng","year":"2015","unstructured":"Zheng H, Lian K, Yang F, Jin Y, Zhu Z, Guo J, Cao W, Liu H, He J, Zhang K, et al. Cross-protective efficacy of engineering serotype A foot-and-mouth disease virus vaccine against the two pandemic strains in swine. Vaccine. 2015;33:5772\u20138.","journal-title":"Vaccine"},{"key":"1394_CR41","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1016\/S0264-410X(02)00148-2","volume":"20","author":"CY Wang","year":"2002","unstructured":"Wang CY, Chang TY, Walfield AM, Ye J, Shen M, Chen SP, Li MC, Lin YL, Jong MH, Yang PC, et al. Effective synthetic peptide vaccine for foot-and-mouth disease in swine. Vaccine. 2002;20:2603\u201310.","journal-title":"Vaccine"},{"key":"1394_CR42","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1016\/j.intimp.2015.08.017","volume":"28","author":"M Fang","year":"2015","unstructured":"Fang M, Wang H, Tang T, Zhao P, Du J, Guo S, Wei H, Xu H, Wan M, Wei X, et al. Single immunization with a recombinant multiple-epitope protein induced protection against FMDV type Asia 1 in cattle. Int Immunopharmacol. 2015;28:960\u20136.","journal-title":"Int Immunopharmacol"},{"key":"1394_CR43","doi-asserted-by":"publisher","first-page":"W294","DOI":"10.1093\/nar\/gks493","volume":"40","author":"J Ko","year":"2012","unstructured":"Ko J, Park H, Heo L, Seok C. GalaxyWEB server for protein structure prediction and refinement. Nucleic Acids Res. 2012;40:W294\u20137.","journal-title":"Nucleic Acids Res"},{"key":"1394_CR44","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1107\/S0907444909042073","volume":"66","author":"VB Chen","year":"2010","unstructured":"Chen VB, Arendall WB 3rd, Headd JJ, Keedy DA, Immormino RM, Kapral GJ, Murray LW, Richardson JS, Richardson DC. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr. 2010;66:12\u201321.","journal-title":"Acta Crystallogr D Biol Crystallogr"},{"key":"1394_CR45","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1016\/j.coviro.2015.04.003","volume":"11","author":"S Li","year":"2015","unstructured":"Li S, Zhang J, Xia N. Lessons from hepatitis E vaccine design. Curr Opin Virol. 2015;11:130\u20136.","journal-title":"Curr Opin Virol"},{"key":"1394_CR46","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/362566a0","volume":"362","author":"D Logan","year":"1993","unstructured":"Logan D, Abu-Ghazaleh R, Blakemore W, Curry S, Jackson T, King A, Lea S, Lewis R, Newman J, Parry N, et al. Structure of a major immunogenic site on foot-and-mouth disease virus. Nature. 1993;362:566\u20138.","journal-title":"Nature"},{"key":"1394_CR47","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1186\/1471-2105-9-514","volume":"9","author":"J Ponomarenko","year":"2008","unstructured":"Ponomarenko J, Bui HH, Li W, Fusseder N, Bourne PE, Sette A, Peters B. ElliPro: a new structure-based tool for the prediction of antibody epitopes. BMC Bioinform. 2008;9:514.","journal-title":"BMC Bioinform"},{"key":"1394_CR48","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1021\/ct300854w","volume":"9","author":"M Jamroz","year":"2013","unstructured":"Jamroz M, Orozco M, Kolinski A, Kmiecik S. Consistent view of protein fluctuations from all-atom molecular dynamics and coarse-grained dynamics with knowledge-based force-field. J Chem Theory Comput. 2013;9:119\u201325.","journal-title":"J Chem Theory Comput"}],"container-title":["Microbial Cell Factories"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12934-020-01394-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12934-020-01394-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12934-020-01394-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T10:06:18Z","timestamp":1650535578000},"score":1,"resource":{"primary":{"URL":"https:\/\/microbialcellfactories.biomedcentral.com\/articles\/10.1186\/s12934-020-01394-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,11]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1394"],"URL":"https:\/\/doi.org\/10.1186\/s12934-020-01394-1","relation":{},"ISSN":["1475-2859"],"issn-type":[{"value":"1475-2859","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,11]]},"assertion":[{"value":"31 July 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 July 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"137"}}