{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T19:17:15Z","timestamp":1793128635103,"version":"4.5.0"},"reference-count":92,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T00:00:00Z","timestamp":1671667200000},"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":["32070923"],"award-info":[{"award-number":["32070923"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2021-I2M-1-043"],"award-info":[{"award-number":["2021-I2M-1-043"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"High-level Talent Promotion and Training Project of Kunming","award":["32070923"],"award-info":[{"award-number":["32070923"]}]},{"name":"High-level Talent Promotion and Training Project of Kunming","award":["2021-I2M-1-043"],"award-info":[{"award-number":["2021-I2M-1-043"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["32070923"],"award-info":[{"award-number":["32070923"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2021-I2M-1-043"],"award-info":[{"award-number":["2021-I2M-1-043"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hand-foot-and-mouth disease (HFMD) is an infectious disease of children caused by more than 20 types of enteroviruses, with most cases recovering spontaneously within approximately one week. Severe HFMD in individual children develops rapidly, leading to death, and is associated with other complications such as viral myocarditis and type I diabetes mellitus. The approval and marketing of three inactivated EV-A71 vaccines in China in 2016 have provided a powerful tool to curb the HFMD epidemic but are limited in cross-protecting against other HFMD-associated enteroviruses. This review focuses on the epidemiological analysis of HFMD-associated enteroviruses since the inactivated EV-A71 vaccine has been marketed, collates the progress in the development of multivalent enteroviruses vaccines in different technical routes reported in recent studies, and discusses issues that need to be investigated for safe and effective HFMD multivalent vaccines.<\/jats:p>","DOI":"10.3390\/ijms24010169","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T02:06:14Z","timestamp":1671674774000},"page":"169","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["Hand-Foot-and-Mouth Disease-Associated Enterovirus and the Development of Multivalent HFMD Vaccines"],"prefix":"10.3390","volume":"24","author":[{"given":"Xinglong","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6352-2469","authenticated-orcid":false,"given":"Heng","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1870-0035","authenticated-orcid":false,"given":"Longding","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Systemic Innovative Research on Virus Vaccine, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1080\/22221751.2021.1906754","article-title":"Viral determinants that drive Enterovirus-A71 fitness and virulence","volume":"10","author":"Ang","year":"2021","journal-title":"Emerg. 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