{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T02:42:18Z","timestamp":1789785738193,"version":"4.0.1"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology of the People\u2019s Republic of China","doi-asserted-by":"publisher","award":["2015ZX09102021"],"award-info":[{"award-number":["2015ZX09102021"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Outbreaks of hand, foot and mouth disease (HFMD) have occurred frequently in the Asian-Pacific region over the last two decades, caused mainly by the serotypes in Enterovirus A species. High-quality monoclonal antibodies (mAbs) are needed to improve the accuracy and efficiency of the diagnosis of enteroviruses associated HFMD. In this study, a mAb 1A11 was generated using full particles of CV-A5 as an immunogen. In indirect immunofluorescence and Western blotting assays, 1A11 bound to the viral proteins of CV-A2, CV-A4, CV-A5, CV-A6, CV-A10, CV-A16, and EV-A71 of the Enterovirus A and targeted VP3. It has no cross-reactivity to strains of Enterovirus B and C. By mapping with over-lapped and truncated peptides, a minimal and linear epitope 23PILPGF28 was identified, located at the N-terminus of the VP3. A BLAST sequence search of the epitope in the NCBI genus Enterovirus (taxid: 12059) protein database indicates that the epitope sequence is highly conserved among the Enterovirus A species, but not among the other enterovirus species, first reported by us. By mutagenesis analysis, critical residues for 1A11 binding were identified for most serotypes of Enterovirus A. It may be useful for the development of a cost-effective and pan-Enterovirus A antigen detection for surveillance, early diagnosis and differentiation of infections caused by the Enterovirus A species.<\/jats:p>","DOI":"10.3390\/v15041028","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T10:11:25Z","timestamp":1682071885000},"page":"1028","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of a Conserved, Linear Epitope on VP3 of Enterovirus A Species Recognized by a Broad-Spectrum Monoclonal Antibody"],"prefix":"10.3390","volume":"15","author":[{"given":"Lie","family":"Fu","sequence":"first","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Ping","family":"Jin","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Wang","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha-Sha","family":"Qian","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Li","family":"Meng","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0916-053X","authenticated-orcid":false,"given":"Shuo","family":"Shen","sequence":"additional","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd., Wuhan 430207, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20909","DOI":"10.1038\/s41598-020-77768-7","article-title":"Epidemical and etiological study on hand, foot and mouth disease following EV-A71 vaccination in Xiangyang, China","volume":"10","author":"Meng","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.46234\/ccdcw2020.044","article-title":"Pathogen spectrum of hand, foot, and mouth disease based on laboratory surveillance\u2014China, 2018","volume":"2","author":"Liu","year":"2020","journal-title":"China CDC Wkly."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s12250-019-00169-2","article-title":"National epidemiology and evolutionary history of four hand, foot and mouth disease-related enteroviruses in China from 2008 to 2016","volume":"35","author":"Fu","year":"2020","journal-title":"Virol. Sin."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"17028","DOI":"10.1038\/s41598-022-21312-2","article-title":"The spatial-temporal distribution and etiological characteristics of hand-foot-and-mouth disease before and after EV-A71 vaccination in Kunming, China, 2017\u20132020","volume":"12","author":"Wang","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_5","first-page":"1615","article-title":"Enteroviruses: Classification, diseases they cause, and approaches to development of antiviral drugs","volume":"82","author":"Nikonov","year":"2017","journal-title":"Biochemistry"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/S1684-1182(10)60056-4","article-title":"Application of a molecular method for the classification of human enteroviruses and its correlation with clinical manifestations","volume":"43","author":"Lo","year":"2010","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1007\/s00705-015-2425-z","article-title":"Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2015)","volume":"160","author":"Adams","year":"2015","journal-title":"Arch. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1007\/s00705-016-2977-6","article-title":"Ratification vote on taxonomic proposals to the International Committee on Taxonomy of Viruses (2016)","volume":"161","author":"Adams","year":"2016","journal-title":"Arch. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1007\/s00705-022-05516-5","article-title":"Recent changes to virus taxonomy ratified by the International Committee on Taxonomy of Viruses (2022)","volume":"167","author":"Walker","year":"2022","journal-title":"Arch. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Brouwer, L., Moreni, G., Wolthers, K.C., and Pajkrt, D. (2021). World-wide prevalence and genotype distribution of enteroviruses. Viruses, 13.","DOI":"10.3390\/v13030434"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Shah, P.N.M., Filman, D.J., Karunatilaka, K.S., Hesketh, E.L., Groppelli, E., Strauss, M., and Hogle, J.M. (2020). Cryo-EM structures reveal two distinct conformational states in a picornavirus cell entry intermediate. PLoS Pathog., 16.","DOI":"10.1101\/2020.01.08.899112"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1038\/s41467-018-07531-0","article-title":"Structures of Coxsackievirus A10 unveil the molecular mechanisms of receptor binding and viral uncoating","volume":"9","author":"Zhu","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1128\/CMR.11.1.202","article-title":"Molecular typing of enteroviruses: Current status and future requirements. The european union concerted action on virus meningitis and encephalitis","volume":"11","author":"Muir","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/291547a0","article-title":"Primary structure, gene organization and polypeptide expression of poliovirus RNA","volume":"291","author":"Kitamura","year":"1981","journal-title":"Nature"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1099\/0022-1317-73-12-3065","article-title":"The molecular biology of poliovaccines","volume":"73","author":"Minor","year":"1992","journal-title":"J. Gen. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1002\/2211-5463.13400","article-title":"Picornavirus translation strategies","volume":"12","author":"Abellan","year":"2022","journal-title":"FEBS Openbio"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0168-1702(95)00048-U","article-title":"Antibody recognition of picornaviruses and escape from neutralization: A structural view","volume":"38","author":"Mateu","year":"1995","journal-title":"Virus Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1099\/0022-1317-67-7-1283","article-title":"Antigenic structure of polioviruses of serotypes 1, 2 and 3","volume":"67","author":"Minor","year":"1986","journal-title":"J. Gen. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhang, Y., Li, H., and Liu, L. (2022). Hand-Foot-and-Mouth Disease-associated enterovirus and the development of multivalent HFMD Vaccines. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010169"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s10096-018-3206-x","article-title":"Hand, foot and mouth disease: Current knowledge on clinical manifestations, epidemiology, aetiology and prevention","volume":"37","author":"Esposito","year":"2018","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s13052-021-01097-2","article-title":"Oral ulcers in children- a clinical narrative overview","volume":"47","author":"Furlano","year":"2021","journal-title":"Ital. J. Pediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/MOP.0000000000000246","article-title":"Hand-foot-and-mouth disease: A new look at a classic viral rash","volume":"27","author":"Nassef","year":"2015","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4","DOI":"10.7774\/cevr.2017.6.1.4","article-title":"Enterovirus 71 infection and vaccines","volume":"6","author":"Yi","year":"2017","journal-title":"Clin. Exp. Vaccine Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1086\/376635","article-title":"Five years\u2019 experience of reverse-transcriptase polymerase chain reaction in daily diagnosis of enterovirus and rhinovirus infections","volume":"37","author":"Vuorinen","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"ref_25","first-page":"238","article-title":"Diagnosis of human enterovirus A71 infection in Malaysia using a commercial IgM-capture enzyme-linked immunosorbent assay and an IgM-colloidal gold immunochromatographic assay","volume":"33","author":"Tan","year":"2016","journal-title":"Trop. Biomed."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1128\/JCM.36.2.589-591.1998","article-title":"Comparison of use of cerebrospinal fluid, serum, and throat swab specimens in diagnosis of enteroviral acute neurological infection by a rapid RNA detection PCR assay","volume":"36","author":"Dewilde","year":"1998","journal-title":"J. Clin. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1097\/01.inf.0000164810.60080.ad","article-title":"Diagnosis and outcomes of enterovirus infections in young infants","volume":"24","author":"Rittichier","year":"2005","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1128\/jcm.34.1.199-201.1996","article-title":"Rapid and sensitive detection of enteroviruses in specimens from patients with aseptic meningitis","volume":"34","author":"Yerly","year":"1996","journal-title":"J. Clin. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/s12985-015-0316-2","article-title":"Validation and utilization of an internally controlled multiplex Real-time RT-PCR assay for simultaneous detection of enteroviruses and enterovirus A71 associated with hand foot and mouth disease","volume":"12","author":"Thanh","year":"2015","journal-title":"Virol. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1128\/JCM.02339-08","article-title":"New molecular detection tools adapted to emerging rhinoviruses and enteroviruses","volume":"47","author":"Tapparel","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1128\/cdli.2.3.385-386.1995","article-title":"Characterization of the recognition site and diagnostic potential of an enterovirus group-reactive monoclonal antibody","volume":"2","author":"Samuelson","year":"1995","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1159\/000150017","article-title":"Clinical and research application of an enterovirus group-reactive monoclonal antibody","volume":"28","author":"Yousef","year":"1987","journal-title":"Intervirology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1002\/jmv.23372","article-title":"Identification and characterization of a monoclonal antibody recognizing the linear epitope RVADVI on VP1 protein of enterovirus 71","volume":"84","author":"Szyporta","year":"2012","journal-title":"J. Med. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1016\/j.vaccine.2013.02.051","article-title":"Identification of conserved neutralizing linear epitopes within the VP1 protein of coxsackievirus A16","volume":"31","author":"Shi","year":"2013","journal-title":"Vaccine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12084","DOI":"10.1128\/JVI.02189-15","article-title":"Single neutralizing monoclonal antibodies targeting the VP1 GH loop of enterovirus 71 inhibit both virus attachment and internalization during viral entry","volume":"89","author":"Ku","year":"2015","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lim, X.F., Jia, Q., Khong, W.X., Yan, B., Premanand, B., Alonso, S., Chow, V.T., and Kwang, J. (2012). Characterization of an isotype-dependent monoclonal antibody against linear neutralizing epitope effective for prophylaxis of enterovirus 71 infection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0029751"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1186\/1743-422X-9-55","article-title":"Characterization and specificity of the linear epitope of the enterovirus 71 VP2 protein","volume":"9","author":"Kiener","year":"2012","journal-title":"Virol. J."},{"key":"ref_38","unstructured":"Standardization Administration of China (2022, September 13). Laboratory Animal-Guideline for Ethical Review of Animal Welfare. Standardization Administration of China, Available online: https:\/\/openstd.samr.gov.cn\/bzgk\/gb\/newGbInfo?hcno=9BA619057D5C13103622A10FF4BA5D14."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e01743-20","DOI":"10.1128\/JVI.01743-20","article-title":"Efficacy of coxsackievirus A5 vaccine candidates in an actively immunized mouse model","volume":"95","author":"Jin","year":"2021","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"199074","DOI":"10.1016\/j.virusres.2023.199074","article-title":"Identification of specific and shared epitopes at the extreme N-terminal VP1 of Coxsackievirus A4, A2 and A5 by monoclonal antibodies","volume":"328","author":"Tian","year":"2023","journal-title":"Virus Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1159\/000150012","article-title":"Derivation and biochemical characterization of an enterovirus group-specific monoclonal antibody","volume":"28","author":"Yousef","year":"1987","journal-title":"Intervirology"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41598-017-18495-4","article-title":"A novel rat CVB1-VP1 monoclonal antibody 3A6 detects a broad range of enteroviruses","volume":"8","author":"Saarinen","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3108","DOI":"10.1128\/JCM.00479-09","article-title":"Monoclonal antibodies to VP1 recognize a broad range of enteroviruses","volume":"47","author":"Miao","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_44","first-page":"1346","article-title":"Generation of anti-CV-A5 polyclonal and monoclonal antibodies and establishment of quantitative antigen ELISA","volume":"37","author":"Zhang","year":"2021","journal-title":"Chin. J. Immunol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/4\/1028\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:20:57Z","timestamp":1760124057000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/4\/1028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":44,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["v15041028"],"URL":"https:\/\/doi.org\/10.3390\/v15041028","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]}}}