{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:10:07Z","timestamp":1767179407945,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pntd.0013847","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000}}],"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3P0151"],"award-info":[{"award-number":["CMRPG3P0151"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3P0152"],"award-info":[{"award-number":["CMRPG3P0152"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"name":"En Chu Kong Hospital","award":["ECKH_W11306"],"award-info":[{"award-number":["ECKH_W11306"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82502675"],"award-info":[{"award-number":["No. 82502675"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2025J011475"],"award-info":[{"award-number":["2025J011475"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Educational Research Project for Young and Middle-aged Teachers in Fujian Province","award":["JZ240078"],"award-info":[{"award-number":["JZ240078"]}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Antivenom remains the standard and most effective treatment for snakebite envenomation, yet batch-to-batch variability in neutralization potency, even under standardized immunization protocols, continues to present a significant challenge in antivenom production worldwide. This issue is particularly evident in the manufacturing of\n                      <jats:italic>Deinagkistrodon acutus<\/jats:italic>\n                      antivenom in Taiwan, where some hyperimmunized equines fail to achieve the required potency despite identical conditions. Previous studies identified a lower antibody titer against acutolysin A\u2014a key metalloproteinase toxin in\n                      <jats:italic>D. acutus<\/jats:italic>\n                      venom\u2014as a potential contributor to reduced efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methodology\/principal findings<\/jats:title>\n                    <jats:p>\n                      In this study, acutolysin A was purified from\n                      <jats:italic>D. acutus<\/jats:italic>\n                      venom using a two-step HPLC workflow, and specific antibodies were isolated from high-potency equine plasma via affinity chromatography. When supplemented into low-potency plasma, these antibodies markedly improved survival in a murine lethality model, providing direct in vivo evidence that anti-acutolysin A antibodies are a critical determinant of antivenom efficacy. To explore strategies for enhancing these antibody levels, we evaluated a supplemental boosting approach in which purified acutolysin A replaced crude venom during later immunization rounds. This regimen significantly increased titers against acutolysin A but reduced immunoreactivity toward other venom proteins, raising concerns about narrowing antigenic breadth.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions\/significance<\/jats:title>\n                    <jats:p>\n                      Collectively, our results highlight anti-acutolysin A antibodies as key determinants of\n                      <jats:italic>D. acutus<\/jats:italic>\n                      antivenom potency and demonstrate that their targeted supplementation can enhance neutralization efficacy, supporting antibody-based enhancement as a potential strategy to improve the potency of\n                      <jats:italic>D. acutus<\/jats:italic>\n                      antivenoms.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pntd.0013847","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:47:07Z","timestamp":1765565227000},"page":"e0013847","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing Deinagkistrodon acutus antivenom potency through acutolysin A-targeted antibody supplementation"],"prefix":"10.1371","volume":"19","author":[{"given":"Chien-Chun","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Shao","family":"Chou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Xiu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung-Chin","family":"Hsiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lichieh Julie","family":"Chu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongyi","family":"Yan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renchao","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiao-Yun","family":"Chao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Xian","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7991-2434","authenticated-orcid":true,"given":"Cho-Ju","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"key":"pntd.0013847.ref001","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s40409-017-0127-6","article-title":"Snakebite envenomation turns again into a neglected tropical disease!","volume":"23","author":"J-P Chippaux","year":"2017","journal-title":"J Venom Anim Toxins Incl Trop Dis"},{"key":"pntd.0013847.ref002","doi-asserted-by":"crossref","first-page":"17063","DOI":"10.1038\/nrdp.2017.63","article-title":"Snakebite envenoming","volume":"3","author":"JM Guti\u00e9rrez","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"pntd.0013847.ref003","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.toxicon.2018.06.084","article-title":"Current technology for the industrial manufacture of snake antivenoms","volume":"151","author":"G Le\u00f3n","year":"2018","journal-title":"Toxicon"},{"issue":"5","key":"pntd.0013847.ref004","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2174\/187152811797200669","article-title":"Antivenoms for snakebite envenomings","volume":"10","author":"JM Guti\u00e9rrez","year":"2011","journal-title":"Inflamm Allergy Drug Targets"},{"issue":"3","key":"pntd.0013847.ref005","article-title":"Snake antivenoms","volume":"41","author":"DG Lalloo","year":"2003","journal-title":"J Toxicol Clin Toxicol"},{"key":"pntd.0013847.ref006","unstructured":"Kuwajima Y. 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