A new human challenge model for testing heat-stable toxin-based vaccine candidates for enterotoxigenic Escherichia coli diarrhea - dose optimization, clinical outcomes, and CD4+ T cell responses

Sunniva Todnem Sakkestad; Hans Steinsland; Steinar Skrede; Kristine Lillebø; Dag Harald Skutlaberg; Anne Berit Guttormsen; Anton Zavialov; Sari Paavilainen; Hanne Søyland; Marianne Sævik; Astrid Rykkje Heien; Marit Gjerde Tellevik; Eileen Barry; Nina Langeland; Halvor Sommerfelt; Kurt Hanevik

doi:10.1371/journal.pntd.0007823

A new human challenge model for testing heat-stable toxin-based vaccine candidates for enterotoxigenic Escherichia coli diarrhea - dose optimization, clinical outcomes, and CD4+ T cell responses

PLoS Negl Trop Dis. 2019 Oct 30;13(10):e0007823. doi: 10.1371/journal.pntd.0007823. eCollection 2019 Oct.

Authors

Sunniva Todnem Sakkestad¹, Hans Steinsland^{2

3}, Steinar Skrede^{1

4}, Kristine Lillebø⁵, Dag Harald Skutlaberg^{1

5}, Anne Berit Guttormsen^{1

6}, Anton Zavialov⁷, Sari Paavilainen⁷, Hanne Søyland⁴, Marianne Sævik⁴, Astrid Rykkje Heien⁴, Marit Gjerde Tellevik⁸, Eileen Barry⁹, Nina Langeland^{1

8

10}, Halvor Sommerfelt^{2

11}, Kurt Hanevik^{1

8}

Affiliations

¹ Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway.
² Centre for Intervention Science in Maternal and Child Health (CISMAC), Centre for International Health, Department of Global Public Health and Primary Care, Faculty of Medicine, University of Bergen, Bergen, Norway.
³ Department of Biomedicine, Faculty of Medicine, University of Bergen, Bergen, Norway.
⁴ Division for Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
⁵ Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
⁶ Department of Anesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.
⁷ Joint Biotechnology Laboratory, Department of Chemistry, University of Turku, Turku, Finland.
⁸ Norwegian National Advisory Unit on Tropical Infectious Diseases, Department of Medicine, Haukeland University Hospital, Bergen, Norway.
⁹ Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, United States of America.
¹⁰ Department of Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway.
¹¹ Norwegian Institute of Public Health, Ministry of Health and Care Services, Oslo, Norway.

Abstract

ClinicalTrials.gov ClinicalTrials.gov, Project ID: NCT02870751.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Antibodies, Bacterial / blood
Bacterial Outer Membrane Proteins / immunology
CD4-Positive T-Lymphocytes / immunology*
Colony Count, Microbial
Diarrhea / microbiology
Diarrhea / prevention & control
Enterotoxigenic Escherichia coli / immunology*
Enterotoxins / immunology*
Escherichia coli Infections / immunology*
Escherichia coli Infections / prevention & control*
Escherichia coli Proteins / immunology
Escherichia coli Vaccines / administration & dosage*
Escherichia coli Vaccines / immunology*
Female
Hot Temperature
Humans
Immunoglobulin A / blood
Immunoglobulin G / blood
Male
Metalloproteases
Volunteers
Young Adult

Substances

Antibodies, Bacterial
Bacterial Outer Membrane Proteins
CsfC protein, E coli
Enterotoxins
Escherichia coli Proteins
Escherichia coli Vaccines
Immunoglobulin A
Immunoglobulin G
Metalloproteases
YghJ protein, E coli

Associated data

ClinicalTrials.gov/NCT02870751

Grants and funding

This work was partly supported by the Research Council of Norway through the Global Health and Vaccination Programme (GLOBVAC) (https://www.forskningsradet.no/en/), project number 234364. The project has received funding from the European Union’s Seventh Framework Programme (https://ec.europa.eu/research/fp7/index_en.cfm) for research, technological development and demonstration under Grant Agreement no 261472-STOPENTERICS. The project was also supported by funding from the Enteric Vaccine Initiative (EVI) (https://www.path.org/) for the R&D project titled “Developing a safe STh-based vaccine for protection against ETEC diarrhoea”. The contribution by HSo and HSt was in part supported by the Centre for Intervention Science in Maternal and Child Health (CISMAC; project number 223269) (https://www.forskningsradet.no/en/), which is funded by the Research Council of Norway through its Centres of Excellence scheme and the University of Bergen (UiB), Norway. The contribution of STS was in part supported by a PhD grant from the University of Bergen, Norway (https://www.uib.no/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.