{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:20:17Z","timestamp":1789618817475,"version":"build-2803163510"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI155457"],"award-info":[{"award-number":["AI155457"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2024,11,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Hemolytic uremic syndrome (HUS) is a systemic sequelae from gastrointestinal infection with Shiga toxin (Stx) producing\n              <jats:italic>Escherichia coli<\/jats:italic>\n              (STEC) that can result in acute kidney injury, lasting renal disease, and death. Despite a window for intervention between hemorrhagic diarrhea and onset of HUS, no specific therapies exist to prevent or treat HUS following STEC infection. Furthermore, there is no way to predict which patients with STEC will develop HUS or any rapid way to determine which Stx variant is present. To address this, we have broadened the therpay to neutralize additional toxin variants. It contains a multimer of nanobodies derived from camelid heavy chain antibody fragments (VHHs). An improved\n              <jats:underline>V<\/jats:underline>\n              HH-based\n              <jats:underline>n<\/jats:underline>\n              eutralizing\n              <jats:underline>a<\/jats:underline>\n              gent (VNA2) is delivered intramuscularly as RNA combined with LION nanoparticles rather than mRNA, that replicates on administration (repRNA), resulting in a rapidly circulating VNA that can bind systemic toxin. The RNA\/VNA2-Stx administered intramuscularly prevents toxicity and death in a mouse model of acute Stx toxicity.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/iai.00239-24","type":"journal-article","created":{"date-parts":[[2024,10,11]],"date-time":"2024-10-11T13:00:19Z","timestamp":1728651619000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["An anti-Shiga toxin VHH nanobody multimer protects mice against fatal toxicosis when administered intramuscularly as repRNA"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4711-1667","authenticated-orcid":false,"given":"Sally R.","family":"Robinson","sequence":"first","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9570-7807","authenticated-orcid":true,"given":"Denise Ann","family":"Dayao","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jhon A.","family":"Medina","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara J.","family":"Martone","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne K.","family":"Yauch","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troy","family":"Hinkley","sequence":"additional","affiliation":[{"name":"HDT Bio Corp., Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse H.","family":"Erasmus","sequence":"additional","affiliation":[{"name":"HDT Bio Corp., Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles B.","family":"Shoemaker","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4429-3856","authenticated-orcid":false,"given":"Saul","family":"Tzipori","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/toxins12020067"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(83)91795-6"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.3.497-503.1999"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.4.926-941.2004"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-015-1017-6"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1089\/fpd.2013.1704"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1106483"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2011.323"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(11)70165-7"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s100960050181"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis299"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.2.612-619.2002"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.8.4607-4613.2005"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/651198"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00190.x"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.2217\/nnm.13.86"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201707678"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-15876-2"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.01.013"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12010059"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.adh3455"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2023.06.017"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abc9396"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.06.011"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01033-13"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2012.00133"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1364026"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1006\/mpat.1993.1006"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-020-0594-x"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00730-15"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0291937"}],"container-title":["Infection and Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00239-24","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/iai.00239-24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T14:02:34Z","timestamp":1731420154000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/iai.00239-24"}},"subtitle":[],"editor":[{"given":"Victor J.","family":"Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,11,12]]},"references-count":31,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2024,11,12]]}},"alternative-id":["10.1128\/iai.00239-24"],"URL":"https:\/\/doi.org\/10.1128\/iai.00239-24","relation":{},"ISSN":["0019-9567","1098-5522"],"issn-type":[{"value":"0019-9567","type":"print"},{"value":"1098-5522","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,12]]},"assertion":[{"value":"2024-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00239-24"}}