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Given our previous report on enteroviruses weakened by the 2\u2009A\u2009S\/T125A mutation, we assessed the potential of the EV\u2010A71 2A\u2010125A mutant as a vaccine candidate to address this challenge. We found that the 2A\u2010125A mutant caused transient mild symptoms, low viral loads, and no significant pathological changes mild pathological changes in hSCARB2\u2010KI mice, producing long\u2010lasting cross\u2010neutralizing antibodies against two EV\u2010A71 wild strains. Pre\u2010exposure to the 2A\u2010125A mutant substantially protected against the EV\u2010A71 Isehara wild\u2010type strain, causing minor pathologies, significantly reducing muscle and lung inflammation, and preventing neurological damage, with reduced viral loads in vivo. Pre\u2010exposure also distinctly suppressed the expression of pro\u2010inflammatory cytokines, correlating to the severity of clinical symptoms. Collectively, the EV\u2010A71 2A\u2010125A mutant was attenuated and could generate a robust and protective immune response, suggesting its potential as a vaccine candidate and global solution for specific enterovirus vaccine development.<\/jats:p>","DOI":"10.1002\/jmv.29838","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T07:43:25Z","timestamp":1722411805000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Enterovirus A71 2A\u2010S125A acts as an attenuated vaccine candidate, indicating a universal approach in developing enterovirus vaccines"],"prefix":"10.1002","volume":"96","author":[{"given":"Peng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Microbiology, School of Basic Medical Sciences Peking University Health Science Center Beijing 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