{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T23:00:51Z","timestamp":1789772451368,"version":"4.0.1"},"reference-count":61,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education","doi-asserted-by":"publisher","award":["FRGS\/1\/2018\/SKK11\/UM\/02\/2"],"award-info":[{"award-number":["FRGS\/1\/2018\/SKK11\/UM\/02\/2"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Hand, foot and mouth disease (HFMD) is a childhood disease caused by enterovirus A71 (EV-A71) and coxsackievirus A16 (CV-A16). Capsid loops are important epitopes for EV-A71 and CV-A16. Seven chimeric EV-A71 (ChiE71) involving VP1 BC (45.5% similarity), DE, EF, GH and HI loops, VP2 EF loop and VP3 GH loop (91.3% similarity) were substituted with corresponding CV-A16 loops. Only ChiE71-1-BC, ChiE71-1-EF, ChiE71-1-GH and ChiE71-3-GH were viable. EV-A71 and CV-A16 antiserum neutralized ChiE71-1-BC and ChiE71-1-EF. Mice immunized with inactivated ChiE71 elicited high IgG, IFN-\u03b3, IL-2, IL-4 and IL-10. Neonatal mice receiving passive transfer of WT EV-A71, ChiE71-1-EF and ChiE71-1-BC immune sera had 100%, 80.0% and no survival, respectively, against lethal challenges with EV-A71, suggesting that the substituted CV-A16 loops disrupted EV-A71 immunogenicity. Passive transfer of CV-A16, ChiE71-1-EF and ChiE71-1-BC immune sera provided 40.0%, 20.0% and 42.9% survival, respectively, against CV-A16. One-day-old neonatal mice immunized with WT EV-A71, ChiE71-1-BC, ChiE71-1-EF and CV-A16 achieved 62.5%, 60.0%, 57.1%, and no survival, respectively, after the EV-A71 challenge. Active immunization using CV-A16 provided full protection while WT EV-A71, ChiE71-1-BC and ChiE71-1-EF immunization showed partial cross-protection in CV-A16 lethal challenge with survival rates of 50.0%, 20.0% and 40%, respectively. Disruption of a capsid loop could affect virus immunogenicity, and future vaccine design should include conservation of the enterovirus capsid loops.<\/jats:p>","DOI":"10.3390\/vaccines11081363","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T10:40:31Z","timestamp":1692009631000},"page":"1363","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Substitution of Coxsackievirus A16 VP1 BC and EF Loop Altered the Protective Immune Responses in Chimera Enterovirus A71"],"prefix":"10.3390","volume":"11","author":[{"given":"Xiu","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4178-2614","authenticated-orcid":false,"given":"Wei","family":"Chong","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center of Theoretical and Computational Physics, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vannajan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Center of Theoretical and Computational Physics, Faculty of Science, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syahril","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia"},{"name":"Comparative Medicine and Technology Unit, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kartini","family":"Jasni","sequence":"additional","affiliation":[{"name":"Comparative Medicine and Technology Unit, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiful","family":"Suarni","sequence":"additional","affiliation":[{"name":"Comparative Medicine and Technology Unit, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6678-8222","authenticated-orcid":false,"given":"David","family":"Perera","sequence":"additional","affiliation":[{"name":"Institute of Health and Community Medicine, Universiti Malaysia Sarawak, Kota Samarahan 94300, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I-Ching","family":"Sam","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7089-0510","authenticated-orcid":false,"given":"Yoke","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur 50603, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.vaccine.2019.09.111","article-title":"Establishment of Asia-Pacific network for enterovirus surveillance","volume":"38","author":"Chiu","year":"2020","journal-title":"J. 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