{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T08:00:24Z","timestamp":1769760024161,"version":"3.49.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"National Science and Technology Council","award":["108-2321-B-006-012, 110-2320-B-006-031-MY3"],"award-info":[{"award-number":["108-2321-B-006-012, 110-2320-B-006-031-MY3"]}]},{"DOI":"10.13039\/501100004737","name":"National Health Research Institutes","doi-asserted-by":"crossref","award":["NHRI IV-112-PP-12"],"award-info":[{"award-number":["NHRI IV-112-PP-12"]}],"id":[{"id":"10.13039\/501100004737","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2024,1,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Enterovirus A71 (EV-A71) can induce severe neurological complications and even fatal encephalitis in children, and it has caused several large outbreaks in Taiwan since 1998. We previously generated VP1 codon-deoptimized (VP1-CD) reverse genetics (rg) EV-A71 viruses (rgEV-A71s) that harbor a high-fidelity (HF) 3D polymerase. These VP1-CD-HF rgEV-A71s showed lower replication kinetics\n            <jats:italic>in vitro<\/jats:italic>\n            and decreased virulence in an Institute of Cancer Research (ICR) mouse model of EV-A71 infection, while still retaining their antigenicity in comparison to the wild-type virus. In this study, we aimed to further investigate the humoral and cellular immune responses elicited by VP1-CD-HF rgEV-A71s to assess the potential efficacy of these EV-A71 vaccine candidates. Following intraperitoneal (i.p.) injection of VP1-CD-HF rgEV-A71s in mice, we observed a robust induction of EV-A71-specific neutralizing IgG antibodies in the antisera after 21 days. Splenocytes isolated from VP1-CD-HF rgEV-A71s-immunized mice exhibited enhanced proliferative activities and cytokine production (IL-2, IFN-\u03b3, IL-4, IL-6, and TNF-\u03b1) upon re-stimulation with VP1-CD-HF rgEV-A71, as compared to control mice treated with adjuvant only. Importantly, administration of antisera from VP1-CD-HF rgEV-A71s-immunized mice protected against lethal EV-A71 challenge in neonatal mice. These findings highlight that our generated VP1-CD-HF rgEV-A71 viruses are capable of inducing both cellular and humoral immune responses, supporting their potential as next-generation EV-A71 vaccines for combating EV-A71 infection.\n          <\/jats:p>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>EV-A71 can cause severe neurological diseases and cause death in young children. Here, we report the development of synthetic rgEV-A71s with the combination of codon deoptimization and high-fidelity (HF) substitutions that generate genetically stable reverse genetics (rg) viruses as potential attenuated vaccine candidates. Our work provides insight into the development of low-virulence candidate vaccines through a series of viral genetic editing for maintaining antigenicity and genome stability and suggests a strategy for the development of an innovative next-generation vaccine against EV-A71.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/jvi.01558-23","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T14:00:14Z","timestamp":1704376814000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["VP1 codon deoptimization and high-fidelity substitutions in 3D polymerase as potential vaccine strategies for eliciting immune responses against enterovirus A71"],"prefix":"10.1128","volume":"98","author":[{"given":"Wen-Sheng","family":"Hsieh","sequence":"first","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0114-0948","authenticated-orcid":false,"given":"Chiao-Hsuan","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-Yu","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dayna","family":"Cheng","sequence":"additional","affiliation":[{"name":"The Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, 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