{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:28:46Z","timestamp":1790234926323,"version":"4.1.0"},"reference-count":59,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:00:00Z","timestamp":1467331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000738","name":"Department of Veterans Affairs","doi-asserted-by":"crossref","award":["5I01BX001469-04"],"award-info":[{"award-number":["5I01BX001469-04"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["2R01AI89894"],"award-info":[{"award-number":["2R01AI89894"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005624","name":"PATH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005624","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Clin Vaccine Immunol"],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Enterotoxigenic\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            (ETEC) strains are a common cause of diarrhea. Extraordinary antigenic diversity has prompted a search for conserved antigens to complement canonical approaches to ETEC vaccine development. EtpA, an immunogenic extracellular ETEC adhesin relatively conserved in the ETEC pathovar, has previously been shown to be a protective antigen following intranasal immunization. These studies were undertaken to explore alternative routes of EtpA vaccination that would permit use of a double mutant (R192G L211A) heat-labile toxin (dmLT) adjuvant. Here, oral vaccination with EtpA adjuvanted with dmLT afforded significant protection against small intestinal colonization, and the degree of protection correlated with fecal IgG, IgA, or total fecal antibody responses to EtpA. Sublingual vaccination yielded compartmentalized mucosal immune responses with significant increases in anti-EtpA fecal IgG and IgA, and mice vaccinated via this route were also protected against colonization. In contrast, while intradermal (i.d.) vaccination achieved high levels of both serum and fecal antibodies against both EtpA and dmLT, mice vaccinated via the i.d. route were not protected against subsequent colonization and the avidity of serum IgG and IgA EtpA-specific antibodies was significantly lower after i.d. immunization compared to other routes. Finally, we demonstrate that antiserum from vaccinated mice significantly impairs binding of LT to cognate GM1 receptors and shows near complete neutralization of toxin delivery by ETEC\n            <jats:italic>in vitro<\/jats:italic>\n            . Collectively, these data provide further evidence that EtpA could complement future vaccine strategies but also suggest that additional effort will be required to optimize its use as a protective immunogen.\n          <\/jats:p>","DOI":"10.1128\/cvi.00248-16","type":"journal-article","created":{"date-parts":[[2016,5,26]],"date-time":"2016-05-26T03:35:15Z","timestamp":1464233715000},"page":"628-637","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["Immunogenicity and Protective Efficacy against Enterotoxigenic Escherichia coli Colonization following Intradermal, Sublingual, or Oral Vaccination with EtpA Adhesin"],"prefix":"10.1128","volume":"23","author":[{"given":"Qingwei","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, Saint Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim J.","family":"Vickers","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, Saint Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1148-697X","authenticated-orcid":false,"given":"James M.","family":"Fleckenstein","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, Saint Louis, Missouri, USA"},{"name":"Molecular Microbiology and Microbial Pathogenesis Program, Washington University School of Medicine, Saint Louis, Missouri, USA"},{"name":"Medicine Service, Veterans Affairs Medical Center, Saint Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60844-2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(15)00151-5"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2009.80.609"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1586\/erv.12.12"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/123.4.378"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3145"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00932-10"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00619-08"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.06.084"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.37.9.2974-2978.1999"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2014.905745"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.4.2245-2258.2006"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07568"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01304-07"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003446"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02473-10"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.03.035"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2004.09.010"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.05.076"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00351-12"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa030595"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006999"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00538-10"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.87"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.2.869-875.2006"},{"key":"e_1_3_3_27_2","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1093\/clinchem\/26.9.1255","article-title":"Kinetic studies of a quantitative single-tube enzyme-linked immunosorbent assay","volume":"26","author":"Tsang VC","year":"1980","unstructured":"Tsang VC, Wilson BC, Maddison SE. 1980. Kinetic studies of a quantitative single-tube enzyme-linked immunosorbent assay. Clin Chem 26:1255\u20131260.","journal-title":"Clin Chem"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00521-12"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.10.069"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.09.073"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.03.095"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.11.020"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00364-12"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003031"},{"key":"e_1_3_3_35_2","first-page":"115","volume-title":"Joint Panel Conference on Cholera and Other Bacterial Enteric Infections","author":"von Mentzer A","year":"2016","unstructured":"von Mentzer A, Sjoling A, Dougan G, Svennerholm A. 2016. Whole genome sequencing of enterotoxigenic Escherichia coli (ETEC)\u2014search for novel colonization factors, p 115\u2013118. In 50th US-Japan Cooperative Medical Sciences Program. Joint Panel Conference on Cholera and Other Bacterial Enteric Infections, Bethesda, MD."},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00264-10"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.8.2637"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050824"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2014.07.013"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302743"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901466"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.26.14626"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1900"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1086\/517407"},{"key":"e_1_3_3_45_2","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1128\/IAI.67.5.2366-2370.1999","article-title":"Avidity as a determinant of the protective efficacy of human antibodies to pneumococcal capsular polysaccharides","volume":"67","author":"Usinger WR","year":"1999","unstructured":"Usinger WR, Lucas AH. 1999. Avidity as a determinant of the protective efficacy of human antibodies to pneumococcal capsular polysaccharides. Infect Immun 67:2366\u20132370.","journal-title":"Infect Immun"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit178"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1086\/524668"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.05.018"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.5.6.799-803.1998"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1894"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm918"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002822"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2015.0142"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00222"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1007\/82_2010_112"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.32253"},{"key":"e_1_3_3_57_2","first-page":"126","volume-title":"Protective efficacy of an enterotoxigenic E. coli fimbrial tip adhesin vaccine given with LTR192G by intradermal vaccination against experimental challenge with CFA\/I-ETEC in adult volunteers","author":"Harro C","year":"2016","unstructured":"Harro C, Gutierrez R, Talaat K, Porter C, Riddle M, Maciel M, Poole S, Laird R, Savarino S. 2016. Protective efficacy of an enterotoxigenic E. coli fimbrial tip adhesin vaccine given with LTR192G by intradermal vaccination against experimental challenge with CFA\/I-ETEC in adult volunteers, p 126\u2013130. In 50th US-Japan Cooperative Medical Sciences Program. Joint Panel Conference on Cholera and Other Bacterial Enteric Infections, Bethesda, MD."},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.12.3.656-667.1975"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.8.3.322-328.1973"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00736.x"}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00248-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/CVI.00248-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:51:51Z","timestamp":1627591911000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00248-16"}},"subtitle":[],"editor":[{"given":"H. F.","family":"Staats","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,7]]},"references-count":59,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2016,7]]}},"alternative-id":["10.1128\/CVI.00248-16"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00248-16","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7]]},"assertion":[{"value":"2016-05-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-05-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}