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Conventional LAVs involve the adaptation of virulent viruses to novel hosts, cell cultures, or suboptimal environments, resulting in a reduction in pathogenicity while retaining immunogenicity. This process entails directed evolution of the virus to enhance its replication efficiency under these modified conditions. In this review, the development of traditional animal\u2010adapted and cold\u2010adapted LAVs is specially discussed. Additionally, the factors that contribute to virus attenuation from a viral lifecycle perspective are summarized. Finally, we propose future directions for next\u2010generation LAVs.<\/jats:p>","DOI":"10.1002\/advs.202407241","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T04:25:15Z","timestamp":1733459115000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Viral Live\u2010Attenuated Vaccines (LAVs): Past and Future Directions"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5690-2690","authenticated-orcid":false,"given":"Yan\u2010Dong","family":"Tang","sequence":"first","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences  Harbin 150069 China"},{"name":"Heilongjiang Provincial Research Center for Veterinary Biomedicine Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences  Harbin 150069 China"},{"name":"Heilongjiang Provincial Key Laboratory of Veterinary Immunology Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences  Harbin 150069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Li","sequence":"additional","affiliation":[{"name":"School of Public Health Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Ji'nan 250117 China"},{"name":"Key Laboratory of Emerging Infectious Diseases in Universities of Shandong Shandong First Medical University &amp; Shandong Academy of Medical Sciences  Tai'an 271000 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue\u2010Hui","family":"Cai","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences  Harbin 150069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yin","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research Institute of Chinese Academy of Agricultural Sciences  Harbin 150069 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00549"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2019.09.001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2023.09.002"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00479-7"},{"key":"e_1_2_7_5_1","first-page":"479","volume":"379","author":"Minor P. 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