Understanding Typhoid Disease After Vaccination
Condition: Typhoid Fever; Enteric Fever; Typhoid
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 infected with typhoid-causing bacteria, the investigators will determine how
      effective a new oral typhoid vaccine (M01ZH09) is in preventing infection. A previously
      licensed oral typhoid vaccine (Ty21a) will be used to make sure the challenge model used
      works properly.
    

Detailed description: 
      Typhoid is a serious infection killing up to 600,000 people every year; it is a frequent
      cause of fever and hospital admission in areas where disease is common. As the infection is
      restricted to humans, it should be possible to eliminate typhoid; better vaccines and ways of
      confirming infection are required in order for this to succeed. We propose to use a recently
      established human typhoid challenge model in order to evaluate a novel oral vaccine candidate
      and to develop new methods for diagnosing typhoid.

      Although there are vaccines available to prevent typhoid, they offer little protection to
      populations where typhoid predominates, especially young children. Currently, the
      effectiveness of vaccines against typhoid cannot be predicted, as measures of protection
      against typhoid are unknown. As a result, implementation of vaccine programmes in disease
      endemic regions currently requires large and expensive trials in each new population,
      significantly delaying programmatic implementation.

      We will use a typhoid challenge model to achieve our goal of accelerating the introduction of
      more effective vaccines into populations with a high burden of disease. Healthy adults will
      be vaccinated with either a novel oral typhoid vaccine or vaccine-placebo prior to being
      infected with the bacteria causing typhoid. This will allow us to measure the effectiveness
      of the vaccine and to identify components of the immune response important in producing
      protection against infection.

      Current methods for confirming typhoid infection are slow and insensitive, particularly in
      endemic regions where the cost of laboratory equipment is prohibitive. In this project, we
      will also explore ways to diagnose typhoid, with the aim of developing tests that are quick,
      reliable and are be cost-effective in resource-poor settings. This would improve individual
      patient management, and allow accurate measurement of disease burden, which is vital to
      improve the efforts of vaccine programmes.
    

Intervention name(s): Vaccine placebo (excipients only); Ty21a; M10ZH09 vaccine
Intervention type(s): Biological; Biological; Biological
Intervention description(s): single oral dose,; 3 oral doses, alternate days; single oral dose
Other intervention name(s): Vivotif; Typhella
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: typhoid vaccine M01ZH09; Ty21a typhoid vaccine