Evaluation of a prototype vaccine against enterotoxigenic Escherichia coli diarrhoea

ISRCTN	ISRCTN23764070
DOI	https://doi.org/10.1186/ISRCTN23764070
Clinical Trials Information System (CTIS)	2009-015741-23
Protocol serial number	EudraCT number: 2009-015741-23, OEV-120
Sponsor	Gothenburg University Vaccine Research Institute (GUVAX) (Sweden)
Funders	PATH (USA), Sahlgrenska University Hospital (Sweden) (ref: LUA/ALF), Swedish Research Council (Sweden)

Submission date: 03/03/2011
Registration date: 18/03/2011
Last edited: 18/03/2011

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Ann-Mari Svennerholm
Scientific

Dept. of microbiology and immunology
University of Gothenburg
Box 435
Gothenburg
40530
Sweden

Phone	+46 (0)31 786 6202
Email	ann-mari.svennerholm@microbio.gu.se

Study information

Primary study design	Interventional
Study design	Three-armed double-blinded randomised single-centre study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Evaluation of the safety and immunogenicity of a prototype enterotoxigenic Escherichia coli (ETEC) vaccine: a three-armed, double-blinded, randomised, single-centre study
Study objectives	Enterotoxigenic E. coli (ETEC) bacteria are known to be a primary cause of traveller's diarrhoea and diarrhoea in children in developing countries. ETEC bacteria produce heat-labile toxin (LT), heat stable toxin (ST) or both toxins and colonise the intestine by means of so called colonisation factors (CFs). The aim of this study is to determine if a new potentially improved prototype ETEC vaccine, consisting of bacteria over-expressing the colonisation factor CFA/I and administered together with a hybrid of the binding subunits of LT and cholera toxin (LTB/CTB), is safe and gives rise to stronger immune responses than a previously tested ETEC vaccine, consisting of a natural CFA/I expressing ETEC strain + CTB.
Ethics approval(s)	1. Independent Ethics Committee in the Gothenburg region (IECGR) in Sweden approved on 26/10/2009, amendment approved 13/03/2010, ref no 570-09 2. Western Institutional Review Board (WIRB) Olympia, Washington, USA approved on 11/05/2010, ref no 20100565
Health condition(s) or problem(s) studied	Enterotoxigenic E. coli (ETEC) diarrhoea
Intervention	Healthy adult volunteers will be immunised with two consecutive doses of two different ETEC vaccines (Vaccine A and Vaccine B) with 12-16 days interval. Vaccine A consists of ETEC bacteria that over-express the colonisation factor CFA/I + LTB/CTB hybrid protein. Vaccine B consists of a previously tested CFA/I expressing ETEC strain + CTB protein. The vaccines will be mixed with a bicarbonate buffer and administered orally. The volunteers will be randomised into three different study arms: First arm: Subjects immunised with 2 doses of Vaccine A Second arm: Subject immunised with 2 doses of Vaccine B Third arm: Subjects immunised with 2 doses of Vaccine B; each dose containing 4 times higher numbers of bacteria and 4 times more LTB/CTB protein compared to the second arm
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Enterotoxigenic E. coli (ETEC) vaccine
Primary outcome measure(s)	1. To evaluate the safety of a new prototype ETEC vaccine (Vaccine A) and to compare the immunogenicity, i.e. intestinal or intestine-derived IgA antibody responses, against CFA/I and LTB, of the new prototype ETEC vaccine with that of a previously tested ETEC strain in combination with CTB (Vaccine B) 1.1. The safety of the vaccines will be determined by evaluation of study diaries throughout the study period, by clinical chemistry and haematology tests (at screening and 7 days after each immunisation) and by physical examination (at screening and on day 42) 1.2. Intestinal antibody responses are based on enzyme-linked immunosorbent assay (ELISA) measurements of specific antibodies in stool extracts (day 0, 7 and 21) 1.3. Intestine-derived antibody responses are based on ELISA measurements of specific antibodies secreted from cultured peripheral blood cells (using the ALS method) or on ELISPOT assay determinations of the numbers of specific antibody secreting cells (ASC) among peripheral blood mononuclear cells (day 0, 7 and 21)
Key secondary outcome measure(s)	1. To evaluate IgA and IgG antibody responses against CFA/I, LTB and CTB in serum as well as specific IgA in those mucosal samples that are not used as primary endpoints 1.1. Serum and intestinal antibody responses are based on enzyme-linked immunosorbent assay (ELISA) measurements of specific antibodies in sera (day 0, 7, 14, 21 and 42) and stool (day 0, 7 and 21), respectively 1.2. Intestine-derived antibody responses are based on ELISA measurements of specific antibodies secreted from cultured peripheral blood cells (using the ALS method) or on enzyme-linked immunosorbent spot (ELISPOT) assay determinations of the numbers of specific antibody secreting cells (ASC) among peripheral blood mononuclear cells
Completion date	01/06/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	55 Years
Sex	All
Target sample size at registration	60
Key inclusion criteria	1. Males or females aged 18-55 years 2. Healthy constitution as established by medical history, medical examination and clinical chemistry and haematology testing 3. Give written informed consent to participate 4. Willing and able to communicate with the investigators and understand the requirements of the study 5. Sexually active females should unless being menopausal agree to use reliable contraception as assessed by the investigator, during 1 month prior to inclusion and one month after the last intake of study vaccine and should have a negative pregnancy test before each vaccination
Key exclusion criteria	1. Has received the oral cholera vaccine Dukoral® in the last 5 years 2. Travelled to ETEC-endemic area within the last 2 years 3. Concomitant intake of immunomodulating drugs during the study period or less than four weeks prior to the first immunisation 4. Vaccination with some other vaccine during the study period or within two weeks prior to trial vaccination 5. Any condition which would limit the subjects ability to complete the study in the opinion of the investigator 6. History of drug or chemical abuse in the year before the study 7. Receipt of any other investigational product in the month before study entry 8. Concomitant participation in any other clinical study 9. Donation of blood 6 weeks before study entry or at any time during the study 10. Females who are pregnant 11. Females who are nursing 12. History of gastrointestinal or systemic inflammatory or autoimmune disease 13. Any known hypersensitivity to any ingredient in the vaccines 14. Gastroenteritis within two weeks prior to vaccination 15. Antibiotic therapy within six weeks prior to the vaccination
Date of first enrolment	12/05/2010
Date of final enrolment	01/06/2011

Locations

Countries of recruitment

Sweden

Study participating centre

Dept. of microbiology and immunology

Gothenburg
40530
Sweden

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes