Understanding Typhoid Disease After Vaccination
|Typhoid Fever Enteric Fever Typhoid||Biological: Vaccine placebo (excipients only) Biological: Ty21a Biological: M10ZH09 vaccine||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Understanding Typhoid Disease After Vaccination: a Single Centre, Randomised, Doubleblind, Placebo Controlled Study to Evaluate M01ZH09 in a Healthy Adult Challenge Model, Using Ty21a Vaccine as a Positive Control.|
- Diagnosis of typhoid fever [ Time Frame: 2 weeks after typhoid challenge ]
Typhoid fever defined as development of Gram negative bacteraemia after day 5 or temperature over 38C persisting for 12 hours or more.
Typhoid challenge defined as ingestion of virulent S. Typhi (Quailes strain).
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||December 2018|
|Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
|Experimental: M01ZH09 vaccine||
Biological: M10ZH09 vaccine
single oral dose
Other Name: Typhella
|Placebo Comparator: Vaccine placebo||
Biological: Vaccine placebo (excipients only)
single oral dose,
3 oral doses, alternate days
Other Name: Vivotif
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01405521
|Oxford Vaccine Group, Centre for Clinical Vaccinology and Tropical Medicine|
|Oxford, United Kingdom|
|Principal Investigator:||Andrew J Pollard||Oxford Vaccine Group, Department of Paediatrics, University of Oxford|