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ETECvac: Development of a vaccine for enterotoxigenic E. coli based on the heat-stable toxin
Enterotoxigenic E. coli (ETEC) expressing the heat-stable toxin (ST) is among the most important causes of diarrheal disease in children less than 5 years of age in low- and middle-income countries. Diarrhea causes ill health and malnutrition, and is the second most common cause of death among children. Currently available prototype ETEC vaccines target colonization factors and the heat-labile toxin, but not ST. They have so far failed to confer adequate protection, and development of an ST-based vaccine has a high priority.
The ETECvac project is based on a unique and comprehensive ST mutational library, established at the University of Bergen (UiB) and Uni Research, which allows an unprecedented detailed study of the toxin's properties. The main aims of the ETECvac project are to design safe and protective ST vaccine candidates, and to establish the first human challenge model for estimating the protective efficacy of an ST vaccine.
The research will be conducted at UiB and Uni Research, in close collaboration with partners at Institut Pasteur, Paris, France, and Indian Institute of Science, Bangalore, India.
- 2021. Two-step functional screen on multiple proteinaceous substrates reveals temperature-robust proteases with a broad-substrate range . Applied Microbiology and Biotechnology. 3195-3209.
- 2020. Use of flavin containing monooxygenases for conversion of trimethylamine in salmon protein hydrolysates. Applied and Environmental Microbiology.
- 2020. Fragment exchange (FX) plasmid tools for CRISPR/Cas9-mediated gene integration and protease production in Bacillus subtilis. Applied and Environmental Microbiology.
- 2019. Virus-like particle-display of the enterotoxigenic Escherichia coli heat-stable toxoid STh-A14T elicits neutralizing antibodies in mice. Vaccine. 6405-6414.
- 2019. Immunizations with enterotoxigenic Escherichia coli heat-stable toxin conjugates engender toxin-neutralizing antibodies in mice that also cross-react with guanylin and uroguanylin. Infection and Immunity. 1-12.
- 2019. From potent toxin to vaccine toxoid: Engineering the enterotoxigenic Escherichia coli heat-stable toxin into a subunit vaccine component.
- 2018. Purification and characterization of native and vaccine candidate mutant enterotoxigenic escherichia coli heat-stable toxins. Toxins. 1-15.
- 2018. Mutational analysis of the pro-peptide of a marine intracellular subtilisin protease supports its role in inhibition. Proteins: Structure, Function, and Bioinformatics. 1-13.
- 2018. Independent losses of a xenobiotic receptor across teleost evolution. Scientific Reports. 1-13.
- 2018. Development of an enterotoxigenic Escherichia coli vaccine based on the heat-stable toxin. Human Vaccines & Immunotherapeutics. 1379-1388.