The purpose of this protocol is to generate a set of data that will be analysed by integrated systems biology approach, for validation in subsequent clinical trials or in animal models. 240 healthy participants (18-45y) will be enrolled, 200 will be administered a dose of Boostrix on Day 0, 20 will receive a placebo on Day 0.
This study is part of the BIOVACSAFE project, a 5-year project funded by the Innovative Medicine Initiative, which will undertake a series of correlated clinical studies that will apply and develop technologies to generate clinical data on inflammation with licensed vaccines as benchmarks, and identify biomarkers to predict acceptable reactogenicity, for correlation with standardized clinical readouts and inflammatory markers assessed in natural infections. The purpose of this protocol is to generate data to undergo integrated systems biology analysis to validate biomarkers identified in the exploratory studies conducted previously or to identify new biomarkers of responses to immunisation The data set will include data characterising: 1. Physiological responses at various time points after immunisation by measuring: * Local and systemic vaccine-related clinical events. * Haematology (blood counts and ESR) and biochemistry parameters. 2. Innate and adaptive immune responses including: * Innate immune activation detected by global gene expression in whole blood * Adaptive humoral immunity determined by the quantification antibodies directed against Tetanus toxoid (TT), Diphteria toxoid (DT), Pertussis toxin (PT), Fimbrial haemagglutinin (FHA) and Pertactin (PTN). * Adaptive immune activation detected by gene pathway activation in whole blood * Metabolic responses as detected by metabolic gene expression and pathway activation in whole blood * Innate and adaptive immune activation detected by measuring the concentration of selected soluble mediators in serum including: chemokines and cytokines and acute phase proteins * As an exploratory endpoint, the adaptive cellular immune response will be evaluated via counting vaccine antigen-specific Cluster of Differentiation 4 (CD4)+ T cells expressing activation markers and/or cytokines following in vitro stimulation and analysis by flow cytometry (and or CyTOF). 3. Genetic testing of subjects when deemed necessary (genetic testing analysis may be SNP (single nucleotide polymorphism) analysis or full genome analysis). 4. Correlations in changes in innate immune activation and metabolism with adverse events, haematology and biochemistry panels, genotype and physiological assessments The investigators will biobank all samples for the duration of the BIOVACSAFE programme so that they can selectively analyse different samples and different time points depending on the results generated, principally from the gene expression analysis of whole blood.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
240
Randomised assignment
Randomised assignment
Center for Vaccinology
Ghent, East-Flanders, Belgium
Frequency of local vaccine-related clinical events
Participants will report these events on a diary, measuring local events or scoring them from 0 (absent) to 3 (severe)
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Frequency of systemic vaccine-related clinical events.
Participants will report these events on a diary, scoring them from 0 (absent) to 3 (severe)
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Physiological assessments: Change from pre-immunisation baseline values in body temperature.
Time frame: Up to 7 days after vaccination
Change from pre-immunisation baseline values in 'Erythrocyte Sedimentation Rate' (ESR)
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in creatinin
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in C Reactive Protein (CRP)
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in aspartate transaminase (AST)/ alanine transaminase (ALT)
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in albumin
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in estimated glomerular filtration rate (eGFR)
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Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in gamma glutamyl transpeptidase (GGT)
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in total protein
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in prothrombin/fibrinogen
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in global gene expression measured on whole blood samples.
Time frame: At selected timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in metabolic gene expression measured on whole blood samples.
Time frame: At selected timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in serum levels of antibodies to vaccine antigens (anti-T, anti-D, anti-PT, anti-FHA and anti-PRN) in serum samples.
Time frame: At selected timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation values of adaptive cellular immune response via enumeration of TT-, DT-, PT-, FHA- and PTN-specific CD3/CD4+ or CD3/CD8+ T cells expressing activation markers/cytokines following IV stimulation and analysis by flow cytometry.
Time frame: At 7 days after vaccination
Change from pre-immunisation baseline values in concentration of selected cytokines and acute phase proteins in serum samples
Time frame: At selected timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in pathway activation measured on whole blood samples.
Time frame: At selected timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in haemoglobin
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in red blood cell count
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in haematocrit
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in white blood cell count
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in platelet count
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in white blood cells
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in 'mean corpuscular volume'
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in 'mean corpuscular heamoglobin'
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in 'mean corpuscular heamoglobin concentration'
Time frame: At all timepoints from vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in Cell Mediated Immunity status in response to in vitro antigen stimulation
Time frame: At all timepoints from vaccination up to 28 days after vaccination