Training Study to Characterize Biomarkers to Chickenpox and Yellow Fever Vaccines
It is thought that vaccines trigger innate inflammatory responses to induce antigenspecific adaptive immunity (the desired effect), but excessive inflammation may lead to serious inflammatory complications or unwanted side effects. Currently there is a lack of reliable biomarkers (a measurable biological response that predicts something) able to predict severe inflammation and this has resulted in the development of several vaccines being terminated and the withdrawal of some licensed vaccines which were associated with inflammatory complications.
This study is part of the BIOVACSAFE project which is a 5year €30M project funded by the Innovative Medicine Initiative. The project involves a series of clinical studies using licensed vaccines as benchmarks to generate clinical data on inflammation and identify biomarkers that can be used to predict acceptable reactogenicity. The target is to identify biomarkers that can predict the occurrence of beneficial and detrimental effects in response to a vaccine. Such biomarkers could be used in future vaccine development programs to optimize selection of vaccine candidates with a profile that will be unlikely to generate worrisome safety signals once they are in generalized use.
This study is one in a series of "training" studies which will each use different licensed vaccines that are prototypical representatives of a class of vaccine used in a particular target population. Forty eight subjects will be randomised into three groups to receive: A) Varicella zoster vaccine (n = 20), B) Yellow Fever vaccine (n = 20), C) Saline placebo (n = 8). Following a screening visit, participants will undergo a seven day residential visit which will include immunization and intensive monitoring of physiological (e.g. heart rate, oral temperature, blood pressure) metabolic and immune (innate and adaptive) parameters. This visit will be followed up by four outpatient visits with further monitoring and blood samples.
|Healthy||Biological: Varicella-zoster virus Biological: Yellow Fever Vaccine Biological: Placebo|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
|Official Title:||A Clinical Study to Generate an Exploratory Training Set of Data Characterising Clinical Events, Physiological and Metabolic Responses, and Innate and Adaptive Immune Responses Following a Single Subcutaneous Immunisation With Either "Varilrix" Varicella-zoster Vaccine, "Stamaril" Yellow Fever Vaccine or Saline Placebo in Healthy Adults With Evidence of Pre-existing Immunity to Varicella-zoster and no Existing Immunity to Yellow Fever.|
- Change from baseline values of global gene expression in whole blood. [ Time Frame: Visits 1 (Day -28 to -2), 2 (Day -1 to +5) , 3 (Day 7), 4 Day 14), 5 (Day 21) and 6 (Day 28). ]
- Proportion of subjects experiencing vaccine-related clinical events following administration of first dose of vaccine. [ Time Frame: Visits 2 (Day -1 to +5) , 3 (Day 7), 4 Day 14), 5 (Day 21) and 6 (Day 28). ]
- Change from baseline values of copy number of yellow fever virus in plasma. [ Time Frame: Visits 2 (Day -1 to +5) , 3 (Day 7), 4 Day 14), 5 (Day 21) and 6 (Day 28). ]
- Change from baseline values in concentration of serum anti-yellow fever antibodies. [ Time Frame: Visits 1 (Day -28 to -2), 2 (Day -1 to +5) , 3 (Day 7), 4 Day 14), 5 (Day 21) and 6 (Day 28). ]
|Study Start Date:||September 2013|
|Study Completion Date:||January 2014|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
Participants receive one dose of 'Varilrix' varicella-zoster vaccine.
Biological: Varicella-zoster virus
Other Name: Varilrix
Participants receive one dose of 'Stamaril' yellow fever vaccine.
Biological: Yellow Fever Vaccine
Other Name: Stamaril
Placebo Comparator: Placebo
Participants receive one injection of placebo.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01765413
|University of Surrey, (Surrey Clinical Research Centre)|
|Guildford, Surrey, United Kingdom, GU2 7XP|
|Principal Investigator:||David J Lewis||University of Surrey|