Vaccines Against Salmonella Typhi

Exclusion Criteria

• •The participant will not be enrolled if any of the following apply:
• •History of significant organ/system disease that could interfere with trial conduct or completion. Including, for example, but not restricted to: Cardiovascular, respiratory, haematological, endocrine, Renal/bladder, biliary tract, gastro-intestinal, neurological, metabolic, autoimmune or infectious disease. Or Psychiatric illness requiring hospitalisation or known or suspected drug and/or alcohol misuse
• •Have any known or suspected impairment of immune function, alteration of immune function, or prior immune exposure that may alter immune function to typhoid infection
• •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 .
• •Weight less than 50kg
• •Presence of implants or prosthesis.
• •Anyone taking long-term medication that may affect symptom reporting or interpretation of the study results.
• •Contraindication to ciprofloxacin or macrolide antibiotics.
• •Female participants who are pregnant, lactating or who are unwilling to ensure that they or their partner use effective contraception one month prior to challenge and continue to do so until two negative stool samples, a minimum of 2 weeks after completion of antibiotic treatment, have been obtained.
• •Occupations involving:
• •* Direct contact with young children attending pre-school groups or nursery or aged under 2 years, or
• •* Direct contact with highly susceptible patients or persons in whom typhoid infection would have particularly serious consequences (unless willing to avoid work until demonstrated not to be infected with typhoid in accordance with guidance from Public Health England)
• •Occupations involving commercial food handling
• •Close household contact with:
• •* Young children (defined as those attending pre-school groups, nursery or those aged less than 2 years)
• •* Immunocompromised individuals
• •Scheduled elective surgery or other procedures requiring general anaesthesia during the study period.
• •Participants who have participated in another research study involving an investigational product within the 30 days prior to enrolment
• •Detection of any abnormal results from screening investigations (at the clinical discretion of the study team).
• •Inability to comply with any of the study requirements
• •Any other social, psychological or health issues which, in the opinion of the study staff, may
• •* Put the participant or their contacts at risk because of participation in the study,
• •* Adversely affect the interpretation of the primary endpoint data,
• •* Impair the participant's ability to participate in the study.
• •Having previously received any typhoid vaccine
• •Having been resident in an enteric fever endemic country for 6 months or more.
• •Have previously been diagnosed with laboratory-confirmed typhoid or paratyphoid infection or been given a diagnosis compatible with enteric fever.
• •Have participated in previous typhoid or paratyphoid challenge studies
• •Have received vaccination with tetanus toxoid containing vaccine within the past 12 months.
• •Have any history of allergy to vaccine components
• •Have a prolonged corrected QT interval (\>450 milliseconds) on ECG screening