Vaccines Against Salmonella Typhi (VAST)
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|ClinicalTrials.gov Identifier: NCT02324751|
Recruitment Status : Active, not recruiting
First Posted : December 24, 2014
Last Update Posted : October 18, 2018
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.
|Condition or disease||Intervention/treatment||Phase|
|Typhoid Fever Enteric Fever||Biological: Vi-TCV Biological: Vi-PS Vaccine Biological: Control (Men ACWY)||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||112 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||A Phase IIb, 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|
|Study Start Date :||September 2015|
|Actual Primary Completion Date :||December 2, 2017|
|Estimated Study Completion Date :||December 2018|
Single intramuscular injection
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
Other Name: Typbar-TCV
Active Comparator: Vi-PS Vaccine
Single intramuscular injection
Biological: Vi-PS Vaccine
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
Other Name: TYPHIM Vi
Control (Men ACWY)
Single intramuscular injection
Biological: Control (Men ACWY)
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 Name: MENVEO
- Clinically or microbiologically proven typhoid infection [ Time Frame: Up to 14 days after typhoid challenge dose administration ]Clinical (fever >38 degrees for more than 12 hours) or microbiologically (blood culture positive) proven typhoid infection following oral challenge with Salmonella Typhi.
- Clinical manifestations of typhoid infection after typhoid challenge as determined by physical examination, participant symptom reporting and microbiological assays [ Time Frame: Clinical signs and solicited symptoms occurring during the 21 day period after challenge; microbiological assays and unsolicited symptoms followed up over the course of one year ]In particular comparing control and typhoid vaccination groups regarding time to onset of symptoms, duration of illness, symptom severity, time to onset of bacteraemia, time to onset of stool shedding, and inflammatory response after typhoid challenge
- Host immune responses (including Geometric Mean Titres of Salmonella Typhi antigen specific antibodies, antigen specific cell frequencies) at baseline, post-vaccination and post-typhoid challenge time points [ Time Frame: From baseline (pre-vaccination) to final follow up visit at one year ]
- Laboratory and high-throughput assays to measure gene expression and protein translation at baseline, post-vaccination and post-challenge time points [ Time Frame: From baseline (pre-vaccination) to 28 days after challenge (total duration 2 months) ]To assess variation in genomic response to vaccination with Vi-TCV, Vi-PS and control vaccine and subsequent Salmonella Typhi challenge
- Exploratory analysis of blood and faeces samples to investigate novel diagnostic methods for detecting Salmonella Typhi infection [ Time Frame: From time of challenge until time of typhoid diagnosis (maximum time frame of 14 days) ]
- Assessment of the number of participants reporting solicited local and systemic reactions, and unsolicited adverse events following vaccination with Vi-TCV [ Time Frame: From time of vaccination until 7 days post-vaccination ]
- Producing an anti-Vi IgG serum standard from volunteers vaccinated with Vi-PS (Vi polysaccharide vaccine) [ Time Frame: From time of vaccination until 4-6 weeks post-vaccination ]Sera obtained at baseline and 4-6 weeks post-vaccination, followed by pooling of post-vaccination sera to form an anti-Vi IgG serum standard
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02324751
|Centre for Clinical Vaccinology and Tropical Medicine|
|Oxford, Oxfordshire, United Kingdom, OX3 7LE|
|Principal Investigator:||Andrew J Pollard, FRCPCH, PhD||Oxford Vaccine Group, The University of Oxford|