{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T21:21:13Z","timestamp":1793308873059,"version":"4.5.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1112376"],"award-info":[{"award-number":["OPP1112376"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Cholera has re-emerged as a major global public health threat. Orally administered attenuated or inactivated vaccines offer protection against enteric pathogens such as\n                    <jats:italic>Vibrio cholerae<\/jats:italic>\n                    , and several World Health Organization-prequalified oral cholera vaccines are used globally as part of international cholera prevention and control measures. However, vaccine effectiveness, particularly in young children in low- and middle-income countries, is often lower than in adults, leaving this vulnerable age group at greater risk of cholera. The heat-labile toxin (LT) of enterotoxigenic\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (ETEC) has strong mucosal adjuvant properties, and in detoxified form (double-mutant LT), it has been shown to safely improve immune responses to protein and somatic lipopolysaccharide antigens in children in Bangladesh who received the oral inactivated whole-cell enterotoxigenic ETEC vaccine ETVAX. Subsequent field trials of ETVAX in children in Zambia and The Gambia have also further demonstrated safety and immunogenicity in this difficult-to-immunize age group. Current concerns about reduced effectiveness of oral cholera vaccines in children led us to re-examine data from an earlier unpublished study conducted to discern for the first time, the adjuvant effects of LT on an orally administered vaccine in humans. The study showed that native LT improved immune responses to a cholera vaccine in adult volunteers. More recent work with double-mutant LT administered with the ETEC whole-cell vaccine ETVAX supports the findings reported here with the oral cholera vaccine Dukoral. These data suggest that modern attenuated versions of native LT, such as double-mutant LT, should be evaluated for improving immune responses to cholera vaccines.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1805998","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T05:24:19Z","timestamp":1776662659000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The case for evaluation of double mutant heat-labile toxin as an adjuvant to improve oral cholera vaccine immunogenicity"],"prefix":"10.3389","volume":"17","author":[{"given":"A. 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