Abstract
There is no licensed vaccine against enterotoxigenic Escherichia coli (ETEC), a major cause of diarrhea-associated morbidity and mortality among infants and children in low-income countries and travelers. The results of this vaccination/challenge study demonstrate strong protection by an attenuated ETEC vaccine candidate, ACE527, when co-administered with a mucosal adjuvant, the double-mutant heat-labile toxin (dmLT) of ETEC. Sixty healthy adults participated in a randomized, placebo-controlled, double-blind study with three doses of lyophilized ACE527 (∼3 × 109 of each strain per dose) administered orally with or without dmLT adjuvant (25 µg/dose). Six months later, 36 of these volunteers and a control group of 21 unvaccinated volunteers were challenged with virulent ETEC strain H10407. The primary outcome was severe diarrhea, defined as passing >800 g of unformed stools during the inpatient period following challenge. The vaccine was well tolerated and induced robust immune responses to key antigens. The protective efficacy (PE) against the primary outcome of severe diarrhea was 65.9% (95% confidence interval [CI] 5.4-87.7, p = 0.003). Among subjects receiving the adjuvanted vaccine, the attack rate of severe diarrhea was 23....Continue Reading
Citations
Jul 31, 2019·Current Opinion in Infectious Diseases·Lorne SchweitzerMichael Libman
Feb 23, 2020·Journal of Pediatric Gastroenterology and Nutrition·Alfredo GuarinoSuporn Treepongkaruna
Apr 5, 2019·MSystems·Tracy H HazenDavid A Rasko
Jun 20, 2020·Gut Microbes·Hyesuk SeoWeiping Zhang
Sep 3, 2020·Pathogens·Saman RiazKurt Hanevik
Sep 29, 2020·NPJ Vaccines·David PoncetMark T Orr
Aug 21, 2019·Infection and Immunity·Milton MacielElizabeth B Norton
Apr 8, 2020·NPJ Vaccines·Pedro Henrique Q S MedeirosRichard L Guerrant
Sep 5, 2019·NPJ Vaccines·Subhra ChakrabortyJames M Fleckenstein
Apr 3, 2020·MSphere·Mallory C KieferJacob P Bitoun
Oct 4, 2020·Applied and Environmental Microbiology·Eric CoxEdward G Dudley
Nov 27, 2020·Scientific Reports·Mandi LiuYan Li
Dec 31, 2020·Vaccines·Hans Van der WekenBert Devriendt
Dec 9, 2020·Infection and Immunity·Eric R HallStephen J Savarino
Dec 3, 2020·International Journal of Molecular Sciences·Shiqi LiuSebastian A J Zaat
Mar 2, 2021·Frontiers in Microbiology·Ali KhalidJonathan R Iredell
Feb 14, 2021·NPJ Vaccines·Pedro Henrique Q S MedeirosRichard L Guerrant
May 1, 2021·Scientific Reports·Astrid von MentzerÅsa Sjöling
May 10, 2021·Vaccine·Ibrahim KhalilA Louis Bourgeois
May 15, 2021·NPJ Vaccines·Addison E StoneElizabeth B Norton
Jun 1, 2021·Frontiers in Immunology·Marjahan AkhtarAnna Lundgren
Jul 3, 2021·Microorganisms·Richard WalkerLouis Bourgeois
Jul 28, 2021·Nature Reviews. Immunology·Ed C Lavelle, Ross W Ward
Aug 5, 2021·Immunity·Amrita BhattacharjeeTimothy W Hand