Enterotoxigenic E. coli (ETEC) diarrhoea Infections and Infestations
Conditions
Interventions
Healthy adult volunteers will be given two consecutive doses of tetravalent ETEC vaccine, with or without dmLT adjuvant, or placebo (vaccine buffer alone) with 12-16 days interval. The tetravalent ETE
Sponsors
University of Gothenburg (Sweden)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female aged 18-45 years 2. Healthy constitution as established by medical history, medical examination and clinical chemistry and haematology testing. 3. Willing and able to communicate with the investigators/physician and understand the requirements of the study 4. Give written informed consent to participate 5. Sexually active females should unless being menopausal agree to use reliable contraception as assessed by the investigator/physician, during 1 month prior to inclusion and one month after the last intake of study vaccine and should have a negative urine pregnancy test at screening and also negative urine pregnancy tests before each vaccination.
Exclusion criteria
Exclusion criteria: 1. An acute or chronic medical condition that, in the opinion of the investigator/physician, would render ingestion of the investigational products unsafe or would interfere with the evaluation of responses. This includes, but is not limited to gastrointestinal diseases and autoimmune diseases. 2. Gastroenteritis within two weeks prior to vaccination 3. Antibiotic therapy within two weeks prior to the vaccination 4. Known Hepatitis A, B, C, and/or HIV infection 5. Concomitant intake of immunomodulating drugs during the study period or less than four weeks prior to the first immunization 6. Psychiatric symptoms and treatments during the last year deemed by the investigator/physician to be relevant for participation in the OEV-121 study. 7. Intends to receive any other vaccine during the study period, or within two weeks prior to trial vaccination 8. Any known hypersensitivity to any ingredient in the vaccines 9. Has received Dukoral or other ETEC or cholera vaccines 10. Brought up in ETEC-endemic areas (e.g., urban and rural areas of Central and South America, Caribbean, most countries in Asia, Africa, etc.). 11. Has travelled to ETEC-endemic areas within the last 3 years or spent > two months in ETEC endemic areas during the last 10 years 12. Intends to travel to ETEC endemic countries during the study period 13. Known or suspected history of drug, chemical or alcohol abuse, as deemed by the investigator/physician 14. Receipt of any other investigational product in the month before study entry or during the study deemed by the investigator/physician to be relevant for the OEV-121 study 15. Concomitant participation in any other clinical study deemed by the investigator/physician to be relevant for the OEV-121 study 16. Intends to donate blood at any time during the study 17. Females who are pregnant 18. Females who are nursing 19. Unable to participate in all study visits 20. Any condition or circumstance which would make the subject unsuitable for participation in the study in the opinion of the investigator/physician
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. To evaluate the safety, reactogenicity, and tolerability of the oral tetravalent ETEC vaccine containing 4 different inactivated E. coli strains over-expressing respectively CFA/I, CS3, CS5 and CS6 and a hybrid LCTBA protein given alone and together with two different dosages of dmLT adjuvant 2. To evaluate intestinal, i.e. fecal secretory IgA (SIgA) antibody responses against CFA/I, CS3, CS5, CS6 and LTB 3. To determine intestine-derived antibody secreting cell (ALS or ELISPOT) IgA responses against CFA/I, CS3, CS5, CS6 and LTB 4. To determine adjuvant effect of dmLT at two different dose levels on vaccine immune responses compared to responses when giving vaccine alone | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. To evaluate serum antibody responses against the vaccine antigens 2. To evaluate intestinal and intestine derived immune responses against O78 LPS The safety of the vaccines will be determined by evaluation of study diaries throughout the study period (day 0-42), by clinical chemistry and hematology tests (at screening and 7 days after each immunization) and by physical examination (at screening and on day 42). Serum and intestinal antibody responses are based on ELISA measurements of specific antibodies in sera (day 0-42) and stool (day 0-28), respectively. 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 0-21). | — |
Countries
Sweden
Outcome results
None listed