Invasive non-typhoid salmonella Infections and Infestations Salmonella infection, unspecified
Conditions
Interventions
This vaccine trial is a participant-observer blinded, randomised placebo-controlled study. Participants are allocated to groups 1, 2 and 3 sequentially. They are considered enrolled once they have rec
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Willing and able to give informed consent for participation in the study 2. Aged between 18 and 55 years inclusive 3. In good health as determined by: 3.1. Medical history 3.2. Physical examination 3.3. Clinical judgment of the investigators 4. (Females) Willing to use effective contraception (such as the oral contraceptive pill, contraceptive implant or barrier methods) from 1 month prior to receiving the first vaccine and for the duration of the study 5. Able to attend the scheduled visits and to comply with all study procedures, including internet access for the recording of diary cards 6. Willing to allow his or her General Practitioner and/or Consultant, if appropriate, to be notified of participation in the study 7. Willing to allow the study team access to medical records for the purposes of eligibility assessment and/or safety follow up during the trial. 8. Willing to provide their national insurance number or passport number to be registered on The Over-Volunteering Prevention System (TOPS)
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 14/09/2022: The participant may not enter the study if any of the following apply: 1. History of significant organ/system disease that could interfere with the trial conduct or completion in the clinical judgement of the investigators. This includes any history of significant disease in the following: 1.2. Cardiovascular disease including congenital heart disease, previous myocardial infarction, valvular heart disease (or history of rheumatic fever), previous bacterial endocarditis, history of cardiac surgery (including pacemaker insertion), personal or family history of cardiomyopathy or sudden adult death 1.3. Respiratory disease such as uncontrolled asthma and chronic obstructive pulmonary disease 1.4. Endocrine disorders such as diabetes mellitus and Addison’s disease 1.5. Significant renal or bladder disease 1.6. Biliary tract disease 1.7. Gastro-intestinal disease such as inflammatory bowel disease, abdominal surgery within the last two years, coeliac disease and liver disease (including hepatitis B or C infection) 1.8. Neurological disease such as seizures and myasthenia gravis 1.9. Haematological disease including coagulation problems 1.10. Metabolic disease such as glucose-6-phosphate dehydrogenase deficiency 1.11. Psychiatric illness requiring hospitalisation 1.12. Depression, anxiety or other psychiatric illness whose severity is deemed clinically significant by the study investigators 1.13. Known or suspected drug and/or alcohol misuse (alcohol misuse defined as an intake exceeding 42 units per week) 1.14. Non-benign cancer, except squamous cell or basal cell carcinoma of the skin and cervical carcinoma in situ 2. Have any known or suspected impairment or alteration of immune function, resulting from, for example: 2.1. Congenital or acquired immunodeficiency (including IgA deficiency) 2.2. Human Immunodeficiency Virus infection or symptoms/signs suggestive of an HIV-associated condition 2.3. Autoimmune disease 2.4. Receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 12 months or long-term systemic corticosteroid therapy (including for more than 7 days consecutively within the previous 3 months). 3. Study significant abnormalities on screening investigations, that are either unlikely to resolve or do not resolve on repeat testing (at the discretion of an Investigator) within the recruitment timeline of the study 4. Have received any oral typhoid vaccination (e.g. Ty21a or M01ZH09) within the last 3 years or a paratyphoid vaccine (as part of a clinical trial) 5. Have participated in previous typhoid or paratyphoid challenge studies (with ingestion of challenge agent). 6. Receipt of a live vaccine within 4 weeks prior to vaccination or a killed vaccine within 7 days prior to vaccination 7. Plan to receive any vaccine other than the study vaccine within 4 weeks after any study vaccination (COVID-19 vaccine exempt, see Section 9.14) 8. Any history of allergy or anaphylaxis to a previous vaccine or vaccine component 9. Receipt of immunoglobulin or any blood product transfusion within 3 months of study start 10. Participation in another research study involving an investigational product or that which may compromise the integrity of the study (e.g. significant volumes of blood already taken in previous study) in the past 12 weeks, or are planning to do so within the trial period 11. Planned donation of blood/blood products outside of t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The recording and assessment of local and systemic adverse events (AE) following and up to 7 days after administration of each vaccine dose: 1. Tenderness and pain at the injection site 2. Induration 3. Redness 4. Swelling 5. Headache 6. Malaise 7. Myalgia 8. Nausea and/or vomiting 9. Diarrhoea 10. Abdominal pain 11. Anorexia 12. Arthralgia 13. Fatigue 14. Fever 15. Blood parameters (haematology/biochemistry) Any unsolicited symptom(s) not listed above in addition to any other AE, serious adverse events (SAE) or serious unexpected serious adverse reactions (SUSAR) thought the trial. Solicited Adverse Events will be captured using an e-diary from Day 0 up to and including 7 days (D6) after vaccination. All adverse events will be captured up to Day 28. This will be done via the e-diary for the first 7 days (D0 to D6) and via study visits and participant phone calls to the study team. AEs which have resulted in medical visits or medication will be captured from enrolment throughout the trial up to the participant last visit. SAEs will be captured from enrolment throughout the trial up to the participant last visit. All adverse events will be graded 1-5: 0: Absence or resolution of symptom 1: Awareness of symptom but tolerated, transient or mild discomfort, little or no medical intervention required 2: Discomfort enough to cause limitation of usual activity, some medical intervention or therapy required 3: Significant interference with daily activity 4: Emergency department visit or hospitalisation 5: Fatality | — |
Secondary
| Measure | Time frame |
|---|---|
| Immunological assays to study immune responses to vaccines, including: 1. Antibody concentration against serovar specific O antigens determined by enzyme-linked immunosorbent assay (ELISA) before and after each dose 2. Serum IgG antibody responses against OAg from S. typhimurium and S. enteritidis in samples from all subjects at each time point (D0, D7, D28, D56, D63, D84, D168, D175, D196, D350) will be analysed by ELISA. Test samples will be analysed at three dilutions and colour change compared with a standard curve made with calibrated human serum pool, included on each assay plate. Anti-OAg responses will be expressed in ELISA units. Plate coating antigens are well characterized OAg purified by GVGH. The analysis will be completed a maximum 8 months after the last participant last visit. | — |
Countries
England, United Kingdom
Contacts
Public ContactOxford Vaccine Group
Outcome results
None listed