{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:40:47Z","timestamp":1784720447782,"version":"3.55.0"},"reference-count":33,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scandinavian BioPharma","award":["204139-101"],"award-info":[{"award-number":["204139-101"]}]},{"name":"Scandinavian BioPharma","award":["348-2013-6615"],"award-info":[{"award-number":["348-2013-6615"]}]},{"name":"Scandinavian BioPharma","award":["SB12-0072"],"award-info":[{"award-number":["SB12-0072"]}]},{"DOI":"10.13039\/501100000278","name":"UK\u2019s Department for International Development","doi-asserted-by":"publisher","award":["204139-101"],"award-info":[{"award-number":["204139-101"]}],"id":[{"id":"10.13039\/501100000278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000278","name":"UK\u2019s Department for International Development","doi-asserted-by":"publisher","award":["348-2013-6615"],"award-info":[{"award-number":["348-2013-6615"]}],"id":[{"id":"10.13039\/501100000278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000278","name":"UK\u2019s Department for International Development","doi-asserted-by":"publisher","award":["SB12-0072"],"award-info":[{"award-number":["SB12-0072"]}],"id":[{"id":"10.13039\/501100000278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["204139-101"],"award-info":[{"award-number":["204139-101"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["348-2013-6615"],"award-info":[{"award-number":["348-2013-6615"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Swedish Research Council","doi-asserted-by":"publisher","award":["SB12-0072"],"award-info":[{"award-number":["SB12-0072"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001729","name":"Swedish Foundation for Strategic Research","doi-asserted-by":"publisher","award":["204139-101"],"award-info":[{"award-number":["204139-101"]}],"id":[{"id":"10.13039\/501100001729","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001729","name":"Swedish Foundation for Strategic Research","doi-asserted-by":"publisher","award":["348-2013-6615"],"award-info":[{"award-number":["348-2013-6615"]}],"id":[{"id":"10.13039\/501100001729","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001729","name":"Swedish Foundation for Strategic Research","doi-asserted-by":"publisher","award":["SB12-0072"],"award-info":[{"award-number":["SB12-0072"]}],"id":[{"id":"10.13039\/501100001729","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>The efficacy of an Oral Whole Cell ETEC Vaccine (OEV) against Travelers\u2019 Diarrhea (TD) was reexamined using novel outcome and immunologic measures. More specifically, a recently developed disease severity score and alternative clinical endpoints were evaluated as part of an initial validation effort to access the efficacy of a vaccine intervention for the first time in travelers to an ETEC endemic area. A randomized, double-blind, placebo-controlled trial followed travelers to Guatemala or Mexico up to 28 days after arrival in the country following vaccination (two doses two weeks apart) with an ETEC vaccine. Fecal samples were collected upon arrival, departure, and during TD for pathogen identification. Serum was collected in a subset of subjects to determine IgA cholera toxin B subunit (CTB) antibody titers upon their arrival in the country. The ETEC vaccine\u2019s efficacy, utilizing a TD severity score and other alternative endpoints, including the relationship between antibody levels and TD risk, was assessed and compared to the per-protocol primary efficacy endpoint. A total of 1435 subjects completed 7\u201328 days of follow-up and had available data. Vaccine efficacy was higher against more severe (\u22655 unformed stools\/24 h) ETEC-attributable TD and when accounting for immunologic take (PE \u2265 50%; p &lt; 0.05). The vaccine protected against less severe (3 and 4 unformed stools\/24 h) ETEC-attributable TD when accounting for symptom severity or change in activity (PE = 76.3%, p = 0.01). Immunologic take of the vaccine was associated with a reduced risk of infection with ETEC and other enteric pathogens, and with lower TD severity. Clear efficacy was observed among vaccinees with a TD score of \u22654 or \u22655, regardless of immunologic take (PE = 72.0% and 79.0%, respectively, p \u2264 0.03). The vaccine reduced the incidence and severity of ETEC, and this warrants accelerated evaluation of the improved formulation (designated ETVAX), currently undergoing advanced field testing. Subjects with serum IgA titers to CTB had a lower risk of infection with ETEC and Campylobacter jejuni\/coli. Furthermore, the TD severity score provided a more robust descriptor of disease severity and should be included as an endpoint in future studies.<\/jats:p>","DOI":"10.3390\/microorganisms11102414","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T07:38:46Z","timestamp":1695800326000},"page":"2414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Efficacy of an Enterotoxigenic Escherichia coli (ETEC) Vaccine on the Incidence and Severity of Traveler\u2019s Diarrhea (TD): Evaluation of Alternative Endpoints and a TD Severity Score"],"prefix":"10.3390","volume":"11","author":[{"given":"Nicole","family":"Maier","sequence":"first","affiliation":[{"name":"PATH, Washington, DC 20001, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon L.","family":"Grahek","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Halpern","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Restrepo","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe","family":"Troncoso","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Shimko","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0069-6904","authenticated-orcid":false,"given":"Olga","family":"Torres","sequence":"additional","affiliation":[{"name":"Laboratorio Diagnostico Molecular, Guatemala City 01009, Guatemala"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Belkind-Gerson","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital Colorado, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9338-5119","authenticated-orcid":false,"given":"David A.","family":"Sack","sequence":"additional","affiliation":[{"name":"Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann-Mari","family":"Svennerholm","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Gustafsson","sequence":"additional","affiliation":[{"name":"Scandinavian Biopharma Holding AB, 171 48 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Sj\u00f6strand","sequence":"additional","affiliation":[{"name":"Scandinavian Biopharma Holding AB, 171 48 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Carlin","sequence":"additional","affiliation":[{"name":"Scandinavian Biopharma Holding AB, 171 48 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Louis","family":"Bourgeois","sequence":"additional","affiliation":[{"name":"PATH, Washington, DC 20001, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7258-1690","authenticated-orcid":false,"given":"Chad K.","family":"Porter","sequence":"additional","affiliation":[{"name":"Naval Medical Research Command, Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"ref_1","unstructured":"Centers for Disease Control and Prevention (2023, June 20). 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