Vaccines Against Salmonella Typhi
Condition: Typhoid Fever; Enteric Fever
MeSH terms: Typhoid Fever; Fever
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed 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.
    

Intervention name(s): Vi-TCV; Vi-PS Vaccine; Control (Men ACWY)
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Each 0.5mL vaccine dose contains 25μg of purified Vi capsular polysaccharide (S. Typhi Ty2 strain) conjugated to non-toxic tetanus toxoid. The vaccine will be administered 28 days prior to typhoid challenge; Each 0.5 mL vaccine dose contains 25 μg of purified Vi capsular polysaccharide (S. Typhi Ty2 strain). The vaccine will be administered 28 days prior to typhoid challenge; Each vaccine dose contains N. meningitidis oligosaccharides (10μg MenA oligosaccharide, 5μg of each of MenC, Men Y and MenW-135 oligosaccharides) conjugated to 32.7 μg to 64.1μg Diphtheria CRM197 protein with residual formaldehyde dose less than 0.30μg. The vaccine will be administered 28 days prior to typhoid challenge
Other intervention name(s): Typbar-TCV; TYPHIM Vi; MENVEO
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention