Vaccines Against Salmonella Typhi (VAST)
Research type
Research Study
Full title
Vaccines Against Salmonella Typhi: a phase IIb, single centre, observer-blind, randomised controlled trial to assess the immunogenicity and protective efficacy of Vi conjugated (Vi-TCV) and unconjugated (Vi-PS) polysaccharide vaccines in preventing typhoid infection compared to a control vaccine (meningococcal ACWY), using a human challenge model of typhoid infection
IRAS ID
162909
Contact name
Andrew Pollard
Contact email
Sponsor organisation
Oxford University Hospitals NHS Foundation Trust
Eudract number
2014-002978-36
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Research Summary
Typhoid fever is an infection caused by a bacterium called 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 programs 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 using a human challenge model of typhoid infection. Healthy adults will be vaccinated with the novel typhoid vaccine, a currently used typhoid vaccine or a ‘control’ vaccine. One month after vaccination, participants will be exposed to 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 these two types of typhoid vaccines, the effect of the vaccines 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.
Summary of Results
"Typhoid fever is a disease of poverty, affecting millions of people worldwide who do not have access to safe water. Although the currently licensed vaccines have been available for decades, few countries have included typhoid vaccination in their routine immunisation schedule. New typhoid vaccines – Vi-conjugate vaccines – such as the investigational vaccine assessed in our study (Vi-TT), have been shown to induce stronger immune responses and can be used in young children. The missing piece of information supporting their use, has been understanding how much protection these types of vaccines provide against disease. The main goal of our study was to answer this particular question by vaccinating healthy adults and then deliberately exposing them to typhoid infection by challenging them with the bacteria.
We found that Vi-TT vaccination significantly reduced the number of typhoid fever cases when compared with control vaccination. Typhoid fever was diagnosed in 13/37 (35%) of Vi-TT participants compared with 24/31 (77%) control participants. This suggests that Vi-TT vaccination prevents 54.6% of typhoid infections. The currently available typhoid vaccine (Vi-PS) prevented 52% of infections, with 13/35 (37%) participants diagnosed with typhoid fever.
While it may appear that the investigational vaccine (Vi-TT) did not protect more individuals than the existing vaccine (Vi-PS), it is likely that our study underestimated the protective effect of the vaccine. When we used other diagnostic criteria to capture typhoid fever cases (e.g. cases similar to those seen in endemic settings), we found that 87.1% of infections were prevented by Vi-TT vaccination and 52.3% by Vi-PS vaccination. In addition, our study showed that Vi-TT vaccination induced higher antibody levels (proteins that target typhoid bacteria), and appeared to be associated with less fever and less severe symptoms in diagnosed participants.
We are continuing our efforts in researching typhoid fever and how best to control it with ongoing challenge studies and our collaboration with the University of Maryland. The Typhoid Vaccine Acceleration Consortium (TyVAC), funded by the Bill and Melinda Gates Foundation, will be conducting large vaccine trials in Nepal, Bangladesh and Malawi using the same investigational vaccine (Vi-TT) that we studied."REC name
South Central - Oxford A Research Ethics Committee
REC reference
14/SC/1427
Date of REC Opinion
9 Dec 2014
REC opinion
Favourable Opinion