Completed Infection & Immunity Digestion, Kidneys & Other Organs

Acceleration of the Development of Vaccines and Diagnostics for Typhoid Fever using a human challenge model.

Funder Wellcome Charity-funded
Recipient organisation University of Oxford
Funding £1.6M
Period Jan 2011 — Sept 2015

In plain English

AI plain-English summary

Typhoid fever kills up to 600,000 people each year, yet diagnosing it in the field relies on inadequate tests, and proving a vaccine works requires huge, expensive field trials. The problem is that researchers lack a simple biological marker—a "correlate of protection"—that tells them whether a vaccine is effective without watching thousands of people get sick. This project will deliberately infect healthy volunteers with *Salmonella* Typhi to build a controlled human infection model. Using that model, the team will test both existing and experimental vaccines to identify those correlates of protection, and will also evaluate new diagnostic tests that detect the bacteria in blood or urine. If successful, this work could unlock a single-dose oral typhoid vaccine currently in development by Emergent Biosolutions, clearing the path to phase III trials. It would also give doctors in endemic regions a reliable diagnostic tool, replacing the guesswork that now hampers treatment and surveillance. The research is applied and translational—its value lies in accelerating vaccine rollout and improving clinical care, not in exploring fundamental biology for its own sake.

View original technical description
Typhoid is an important infection of humans causing up to 600,000 deaths/year and is a major cause of travel-related infection. Development of effective vaccines against typhoid and other enteric pathogens is hampered by the absence of a known correlate of protection and large expensive field trials are required to demonstrate efficacy, increasing commercial risk and slowing development. Furthermore diagnosis of typhoid is difficult in many endemic areas where local staff currently rely on inadequate tests. In this study proposal, a model of infection with S. Typhi in healthy volunteers will be established and the model will be used To investigate the pathogenesis and immunobiology of enteric fever and, using both novel and licensed vaccines, to identify correlates of protection and allow extrapolation of clinical trial data from field trials to broader implementation of vaccines. To drive development of a single dose live oral typhoid vaccine, which is in the pipeline of Emergent Biosolutions, by unlocking the decision path to phase III trials. To allow the precise tracking of infection using cultures of blood and stool, thereby Science CONFIDENTIAL 7 CONFIDENTIAL providing an ideal setting for evaluation of the sensitivity of the novel diagnostic assays using blood and urine.

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Researchers

Andrew Pollard (EPMC Awardee)

Related Research

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Original classification

Strategic Translation Award

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