Evaluation of a prototype vaccine against enterotoxigenic Escherichia coli diarrhoea

ISRCTN ISRCTN23764070
DOI https://doi.org/10.1186/ISRCTN23764070
EudraCT/CTIS number 2009-015741-23
Secondary identifying numbers EudraCT number: 2009-015741-23, OEV-120
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

Study designThree-armed double-blinded randomised single-centre study
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details below to request a patient information sheet
Scientific titleEvaluation of the safety and immunogenicity of a prototype enterotoxigenic Escherichia coli (ETEC) vaccine: a three-armed, double-blinded, randomised, single-centre study
Study objectivesEnterotoxigenic 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) studiedEnterotoxigenic E. coli (ETEC) diarrhoea
InterventionHealthy 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 typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Enterotoxigenic E. coli (ETEC) vaccine
Primary outcome measure1. 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)
Secondary outcome measures1. 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
Overall study start date12/05/2010
Completion date01/06/2011

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
Upper age limit55 Years
SexBoth
Target number of participants60
Key inclusion criteria1. 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 criteria1. 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 subject’s 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 enrolment12/05/2010
Date of final enrolment01/06/2011

Locations

Countries of recruitment

  • Sweden

Study participating centre

Dept. of microbiology and immunology
Gothenburg
40530
Sweden

Sponsor information

Gothenburg University Vaccine Research Institute (GUVAX) (Sweden)
University/education

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

Phone +46 (0)31 786 6201
Email jan.holmgren@microbio.gu.se
ROR logo "ROR" https://ror.org/01tm6cn81

Funders

Funder type

Other

PATH (USA)
Government organisation / Other non-profit organizations
Alternative name(s)
Program for Appropriate Technology in Health
Location
United States of America
Sahlgrenska University Hospital (Sweden) (ref: LUA/ALF)

No information available

Swedish Research Council (Sweden)
Government organisation / National government
Alternative name(s)
Swedish Research Council, VR
Location
Sweden

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan