A Combination Vaccine Consisting of Three Live Attenuated Enterotoxigenic Escherichia coli Strains Expressing a Range of Colonization Factors and Heat-Labile Toxin Subunit B Is Well Tolerated and Immunogenic in a Placebo-Controlled Double-Blind Phase I Trial in Healthy Adults
- 1 December 2011
- journal article
- research article
- Published by American Society for Microbiology in Clinical and Vaccine Immunology
- Vol. 18 (12), 2118-2127
- https://doi.org/10.1128/cvi.05342-11
Abstract
Immune responses against colonization factors (CFs) and the nontoxic B component of the enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LTB) are considered to be important for immunity against diarrhea caused by ETEC. Individual live attenuated ETEC derivatives that have had their toxin genes removed and whose aroC , ompC , and ompF genes are deleted have shown promise as vaccines against ETEC. The development of such strains has culminated in the testing of a three-strain-combination live attenuated vaccine known as ACE527, comprised of strains ACAM2025 expressing colonization factor antigen I (CFA/I) and LTB; ACAM2022, expressing CS5, CS6, and LTB; and ACAM2027, expressing CS1, CS2, CS3, and LTB. The recombinant CF and LTB genes expressed in the three strains were inserted into the bacterial chromosome to ensure their stable inheritance and expression without the requirement for any selection. ACE527 has been tested in a randomized placebo-controlled, double-blind, phase I safety and immunogenicity study in healthy adult volunteers and proved to be well tolerated and immunogenic at dose levels of 10 10 and 10 11 total CFU. There was no indication of strain interference on the basis of fecal shedding patterns, with all three being detected in the feces of 50% and 83% of low- and high-dose vaccine recipients, respectively. Similarly, strong immune responses to LTB and to CFs expressed on all three constituent strains were induced, with at least 50% of subjects in the high-dose group responding to LTB, CFA/I, CS3, and CS6.Keywords
This publication has 42 references indexed in Scilit:
- Generation and Characterization of a Live Attenuated Enterotoxigenic Escherichia coli Combination Vaccine Expressing Six Colonization Factors and Heat-Labile Toxin Subunit BClinical and Vaccine Immunology, 2011
- Refinement of a Human Challenge Model for Evaluation of Enterotoxigenic Escherichia coli VaccinesClinical and Vaccine Immunology, 2011
- Prolonged Episodes of Acute Diarrhea Reduce Growth and Increase Risk of Persistent Diarrhea in ChildrenGastroenterology, 2010
- Global, regional, and national causes of child mortality in 2008: a systematic analysisThe Lancet, 2010
- Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled field trialThe Lancet, 2008
- Enteric infections, diarrhea, and their impact on function and developmentJCI Insight, 2008
- Economic Aspects of Travelers’ DiarrheaJournal of Travel Medicine, 2008
- Disease Burden Due to Enterotoxigenic Escherichia coli in the First 2 Years of Life in an Urban Community in BangladeshInfection and Immunity, 2007
- Genetically modified enterotoxigenic Escherichia coli vaccines induce mucosal immune responses without inflammationGut, 2007
- Immune Response, Ciprofloxacin Activity, and Gender Differences after Human Experimental Challenge by Two Strains of Enterotoxigenic Escherichia coliInfection and Immunity, 2007