Placebo Controlled Study to Generate Data Characterising Safety Parameters and Immune Responses
Condition: Prevention of Infections With Bordetella Pertussis
MeSH terms: Whooping Cough
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Boostrix; Placebo (Saline)
Intervention type(s): Biological; Biological
Intervention description(s): Randomised assignment; Randomised assignment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science