A study in healthy volunteers testing a new vaccine against Typhoid and Paratyphoid A infection. Infections and Infestations
Conditions
Interventions
The study will recruit 200 participants, randomised 1:1 to receive a single intramuscular dose of 0.5mL of either:
• The test vaccine (SII TCV(B)) - a bivalent conjugate vaccine against Salmonella Typ
• The comparator vaccine (Typhim Vi) - a licensed vaccine against Salmonella Typhi manufactured by Sanofi Pasteur.
28 days after vaccination, participants will be challenged with Salmonella Paratyphi
Sponsors
University of Oxford
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Inclusion criteria
Inclusion criteria: Participants must satisfy all of the following criteria to be considered eligible for the study: 1. Willing and able to give informed consent for participation in the study 2. Aged between 18 and 55 years, inclusive, at time of vaccination 3. In good health as determined by medical history, physical examination and clinical judgement of the study team 4. Willing to be available at designated site for all required appointments 5. Agree (in the study team’s opinion) to comply with all study requirements, including capacity to adhere to good personal hygiene and infection control precautions 6. Agree to allow study staff to contact their GP to access the participant’s vaccination records, medical history and have their opinion solicited as to the participant’s appropriateness for inclusion 7. Agree to allow study staff to access NHS health records (medical and vaccination history) as required for study purposes 8. Agree to allow their GP (and/or Consultant if appropriate), to be notified of participation in the study 9. Agree to allow national public health agency to be informed of their participation in the study 10. Agree to give their close household contacts written information about the participants’ involvement in the study and offering them voluntary screening for S. Paratyphi A carriage 11. Agree to have 24-hour contact with study staff during the four weeks post challenge and are able to ensure that they are contactable by mobile phone for the duration of the vaccination and challenge period until antibiotic completion 12. Have internet access to allow completion of the e-diary and real-time safety monitoring 13. Agree to avoid antipyretic/anti-inflammatory treatment from challenge until advised by a study doctor or until 14 days after the challenge 14. Agree to refrain from donating blood for the duration of the study 15. Agree to provide their National Insurance/Passport number for the purposes of TOPS registration and for payment of reimbursement expenses 16. Agree to not receive any inactivated vaccine within 7 days before and after vaccination and 7 before and 21 days after challenge 17. Agree to not receive any live vaccine or vaccine containing DT or TT within 28 days before vaccination to 28 days after challenge 18. For participants of childbearing potential: willing to ensure that they or their partner use effective contraception 30 days prior to vaccination and continue to do so until clearance is confirmed
Exclusion criteria
Exclusion criteria: The participant will not be eligible if any of the following apply: 1. History of significant organ/system disease that could interfere with study conduct or completion, in the opinion of the study team. Including, for example, but not restricted to: 1.1. Cardiovascular disease 1.2. Respiratory disease 1.3. Haematological disease 1.4. Endocrine disorders 1.5. Renal or bladder disease, including history of renal calculi 1.6. Biliary tract disease, including biliary colic, asymptomatic gallstones or polyps or previous cholecystectomy 1.7. Gastrointestinal disease including chronic diarrhoea, inflammatory bowel disease, irritable bowel syndrome or diseases requiring the use of regular antacids, H2-receptor antagonists, proton pump inhibitors, laxatives or prokinetic agents 1.8. Neurological disease 1.9. Metabolic disease 1.10. Psychiatric illness requiring hospitalisation, or history of schizophrenia and manic depressive psychosis 1.11. Known or suspected drug use 1.12. Known or suspected alcohol misuse 1.13. Infectious disease 1.14. Coagulation disorders 2. Have any known or suspected impairment of immune function, alteration of immune function or prior immune exposure that may alter immune function resulting from, for example: 2.1. Congenital or acquired immunodeficiency, including IgA deficiency 2.2. History of auto-immune disease 2.3. Human Immunodeficiency Virus or symptoms/signs suggestive of an HIV-associated condition 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 3. Receipt of immunoglobulin or any blood product transfusion within 3 months of study vaccination 4. History of cancer (except squamous cell or basal cell carcinoma of the skin and cervical carcinoma in situ) 5. HLA-B27 positive 6. Moderate or severe depression or anxiety as classified by the Hospital Anxiety and Depression Score at screening or challenge that is deemed clinically significant by the study doctors 7. Weight less than 50 kg 8. Presence of implants or prosthetic material 9. Taking long-term medication (e.g. analgesia, anti-inflammatories or antibiotics) that may affect symptom reporting or interpretation of the study results or that may interact with antibiotics used for the treatment of paratyphoid A (in particular drugs that could prolong corrected QT interval). 10. Contraindication to fluoroquinolones, macrolide antibiotics, co-trimoxazole or ceftriaxone 11. Family history of aneurysmal disease 12. Participants who are pregnant, lactating or who are unwilling to ensure that they or their partner use effective contraception 30 days prior to vaccination and continue to do so until three negative stool samples have been obtained after completion of antibiotic treatment 13. Full-time, part-time or voluntary occupations involving the below (unless willing to avoid work from challenge day until demonstrated not to be infected with S. Paratyphi A by clearance samples in accordance with guidance from national public health agency and willing to allow study staff to inform their employer): 13.1. Direct contact with young children (defined as those attending preschool groups or nursery or aged under 2 years, or 13.2. Direct contact with highly susceptible patients or persons in whom paratyphoid A infection would have particularly serious consequences 13.3. Commercial food handling (involving preparing or serving unw
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The proportion of participants developing S. Paratyphi A infection within 14 days following the challenge (in case any of the pre-specified criteria as mentioned under the Intervention section (Challenge Visits) are satisfied) 2. The Geometric Mean Concentration of S. Typhi Vi antigen-specific IgG measured by ELISA at day 28 following vaccination | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Occurrence of local solicited events in the 7 days following vaccination, systemic solicited events in the 7 days following vaccination, unsolicited events in the 28 days following vaccination and serious adverse events following vaccination throughout study participation. These will be measured using data recorded in the vaccination e-diary by participants and AEs and SAEs will be recorded and reviewed at all visits. 2. Quantification of S. Paratyphi A antigen-specific antibodies measured using in-house ELISA and/or Luminex-based quantification at 28 days following vaccination, including anti-LPS IgG, IgA and IgM and SBA titres 3. Quantification of S. Typhi antigen-specific antibodies measured using ELISA at 28 days following vaccination, for anti-Vi IgG and IgA | — |
Countries
England, United Kingdom, Wales
Contacts
Public ContactSophie Vernon
Outcome results
None listed