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Using an established model of human typhoid infection, whereby healthy adults are deliberately exposed to typhoid-causing bacteria, the investigators will determine how effective a new typhoid conjugate vaccine (Vi-TCV) is in preventing infection. The new typhoid vaccine will be compared with a control vaccine (meningococcal ACWY). The protective effect of a currently used typhoid polysaccharide vaccine (Vi-PS) will also be studied and compared with the control vaccine using this model of typhoid infection.
A second component of this study will involve vaccinating 15-20 participants with Vi-PS. Serum will be obtained prior to vaccination and 4-6 weeks after vaccination. The post-vaccination serum will be pooled and used to create an anti-Vi IgG serum standard.
Full description
Typhoid fever is an infection caused by a bacterium, Salmonella Typhi, that only causes disease in humans. It is transmitted faecal-orally and causes more than 22 million infections every year in developing countries, such as areas of Asia, Africa and South America, where access to clean drinking water and sanitation facilities is limited. Although typhoid fever is treatable with effective antibiotics, there are more than 200,000 deaths every year in these resource-limited regions.
Salmonella Typhi could be eradicated but improving sanitation and living conditions in endemic regions is difficult. Vaccination to prevent the transmission of Salmonella Typhi could significantly reduce the burden of disease. The currently licensed typhoid vaccines are only moderately effective in preventing infection in people who have been immunised and no vaccines are licensed for use in young children. Novel typhoid vaccines have been developed to overcome these problems, but more research and information is needed to study how well these vaccines work before they can be routinely used.
This study proposes to investigate the protective effect of a novel typhoid vaccine (typhoid Vi polysaccharide capsule - tetanus toxoid conjugate vaccine) using a human challenge model of typhoid infection. Healthy adults will be vaccinated with the novel typhoid vaccine, a currently used typhoid vaccine (Vi polysaccharide capsule vaccine) or a control vaccine. One month after vaccination, participants will be exposed to live Salmonella Typhi by drinking a solution containing the bacteria. Participants will then be closely monitored to determine which participants develop infection and which are protected. In addition to assessing the protective effect of conjugated and unconjugated typhoid vaccines, the effect the vaccines have on the immune system and on the clinical course of typhoid infection will also be studied.
It is hoped that the knowledge gained from this study will contribute to the use of vaccines against Salmonella Typhi to help control this preventable disease.
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Inclusion criteria
Participants must satisfy all of the following criteria to be considered eligible for the study:
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:
Occupations involving commercial food handling
Close household contact with:
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
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
Primary purpose
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Interventional model
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112 participants in 3 patient groups
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Data sourced from clinicaltrials.gov
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