A phase II, multicentre, double-blind, randomised, controlled study of a bivalent conjugate vaccine against Salmonella enterica serovar Typhi and Paratyphi A to evaluate the efficacy, immunogenicity and safety using a human challenge model of Paratyphoid A infection
A study in healthy volunteers testing a new vaccine against Typhoid and Paratyphoid A infection.
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 Typhi and Paratyphi A developed and manufactured by the Serum Institute of India or; • 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 A, manufactured by GenIbet BioPharmaceuticals. Vaccination and post-vaccination visits Vaccine randomisation will be completed at the vaccination visit (D-28) using a web-based randomisation system. Participants will also complete an interim medical assessment, check vital signs, complete a urine pregnancy test for participants of childbearing potential, and provide blood and stool samples. Saliva samples will be collected from a subset of participants. Participants will then be vaccinated with either the test vaccine (SII TCV (B)) or comparator (Typhim Vi) according to the randomisation. The research team will give participants access to a web-based electronic diary (e-diary), and a thermometer to take daily temperatures. Participants are asked to record their temperatures twice daily and answer if they had pre-specified solicited symptoms, use of medication and any additional fevers for 7 days after vaccination. They will also have access to input additional symptoms into the diary for 28 days after receiving the vaccine. After receiving the vaccine, participants will be seen after one week (D-21) and two weeks (D-14) for post-vaccination visits during which additional blood samples will be collected from all participants, and stool and saliva samples collected in a subset of participants. Around 28 days after vaccination, participants will be seen in the clinic (post-vaccine immunology visit) for a blood test - this visit may be combined with the pre-challenge visit (D-2) if the visit win
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 expense
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 tha