{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:34:54Z","timestamp":1791153294505,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The striking feature of enterohemorrhagic Escherichia coli (EHEC) infections is the production of Shiga toxins (Stx) implicated in the development of the life-threatening hemolytic uremic syndrome. Despite the magnitude of the social impact of EHEC infections, no licensed vaccine or effective therapy is available for human use. One of the biggest challenges is to develop an effective and safe immunogen to ensure nontoxicity, as well as a strong input to the immune system to induce long-lasting, high-affinity Abs with anti-Stx\u2013neutralizing capacity. The enzyme lumazine synthase from Brucella spp. (BLS) is a highly stable dimer of pentamers and a scaffold with enormous plasticity on which to display foreign Ags. Taking into account the advantages of BLS and the potential capacity of the B subunit of Stx2 to induce Abs that prevent Stx2 toxicity by blocking its entrance into the host cells, we engineered a new immunogen by inserting the B subunit of Stx2 at the amino termini of BLS. The resulting chimera demonstrated a strong capacity to induce a long-lasting humoral immune response in mice. The chimera induced Abs with high neutralizing capacity for Stx2 and its variants. Moreover, immunized mice were completely protected against i.v. Stx2 challenge, and weaned mice receiving an oral challenge with EHEC were completely protected by the transference of immune sera. We conclude that this novel immunogen represents a promising candidate for vaccine or Ab development with preventive or therapeutic ends, for use in hemolytic uremic syndrome\u2013endemic areas or during future outbreaks caused by pathogenic strains of Stx-producing E. coli.<\/jats:p>","DOI":"10.4049\/jimmunol.1300999","type":"journal-article","created":{"date-parts":[[2013,8,6]],"date-time":"2013-08-06T05:33:19Z","timestamp":1375767199000},"page":"2403-2411","source":"Crossref","is-referenced-by-count":53,"title":["Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice"],"prefix":"10.1093","volume":"191","author":[{"given":"Mar\u00eda P","family":"Mejias","sequence":"first","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Academia Nacional de Medicina , Buenos Aires C1425AUM,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giselle","family":"Ghersi","sequence":"additional","affiliation":[{"name":"INMUNOVA S.A. , Buenos Aires C1405BWE,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricio O","family":"Craig","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n Instituto Leloir, Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires \u2013 Consejo Nacional de Investigaciones Cientificas y Tecnicas , Buenos Aires C1405BWE,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia A","family":"Panek","sequence":"additional","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Academia Nacional de Medicina , Buenos Aires C1425AUM,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia V","family":"Bentancor","sequence":"additional","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Academia Nacional de Medicina , Buenos Aires C1425AUM,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariela","family":"Baschkier","sequence":"additional","affiliation":[{"name":"Servicio de Fisiopatogenia, Instituto Nacional de Enfermedades Infecciosas \u2013 Administraci\u00f3n Nacional de Laboratorios e Institutos de Salud \u201cDr. Carlos G. Malbr\u00e1n,\u201d Buenos Aires 1281,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando A","family":"Goldbaum","sequence":"additional","affiliation":[{"name":"INMUNOVA S.A. , Buenos Aires C1405BWE,","place":["Argentina"]},{"name":"Fundaci\u00f3n Instituto Leloir, Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires \u2013 Consejo Nacional de Investigaciones Cientificas y Tecnicas , Buenos Aires C1405BWE,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanesa","family":"Zylberman","sequence":"additional","affiliation":[{"name":"INMUNOVA S.A. , Buenos Aires C1405BWE,","place":["Argentina"]},{"name":"Fundaci\u00f3n Instituto Leloir, Instituto de Investigaciones Bioqu\u00edmicas de Buenos Aires \u2013 Consejo Nacional de Investigaciones Cientificas y Tecnicas , Buenos Aires C1405BWE,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina S","family":"Palermo","sequence":"additional","affiliation":[{"name":"Laboratorio de Patog\u00e9nesis e Inmunolog\u00eda de Procesos Infecciosos, Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Academia Nacional de Medicina , Buenos Aires C1425AUM,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,9,1]]},"reference":[{"key":"2025032405273579100_r1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/nrmicro818","article-title":"Pathogenic Escherichia coli","volume":"2","author":"Kaper","year":"2004","journal-title":"Nat. Rev. Microbiol."},{"key":"2025032405273579100_r2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1128\/CMR.2.1.15","article-title":"Infection by verocytotoxin-producing Escherichia coli","volume":"2","author":"Karmali","year":"1989","journal-title":"Clin. Microbiol. Rev."},{"key":"2025032405273579100_r3","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1051\/vetres:2005002","article-title":"Enterohaemorrhagic Escherichia coli: emerging issues on virulence and modes of transmission","volume":"36","author":"Caprioli","year":"2005","journal-title":"Vet. Res."},{"key":"2025032405273579100_r4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/oxfordjournals.epirev.a036079","article-title":"The epidemiology of infections caused by Escherichia coli O157:H7, other enterohemorrhagic E. coli, and the associated hemolytic uremic syndrome","volume":"13","author":"Griffin","year":"1991","journal-title":"Epidemiol. Rev."},{"key":"2025032405273579100_r5","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0891-5520(05)70217-8","article-title":"Shigella and Shiga toxin-producing Escherichia coli causing bloody diarrhea in Latin America","volume":"14","author":"L\u00f3pez","year":"2000","journal-title":"Infect. Dis. Clin. North Am."},{"key":"2025032405273579100_r6","first-page":"27","article-title":"[The epidemiology of hemolytic uremic syndrome in Argentina. Diagnosis of the etiologic agent, reservoirs and routes of transmission]","volume":"66","author":"Rivas","year":"2006","journal-title":"Medicina (B. Aires)"},{"key":"2025032405273579100_r7","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1159\/000171588","article-title":"Enterohemorrhagic Escherichia coli: a family of emerging pathogens","volume":"15","author":"No\u00ebl","year":"1997","journal-title":"Dig. 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