Placebo Controlled Study to Generate Data Characterising Clinical Events, Physiological Responses and Immune Responses
Condition: Safety Markers of Adjuvanted Influenza Vaccine
MeSH terms: Influenza, Human
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, 228 will be administered a dose of Fluad
      on Day 0, 12 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 a set of data that will be analysed by integrated
      systems biology approach, for validation in subsequent clinical trials or in animal models.
      The dataset will broadly characterise:

        1. Physiological responses at various time points after immunisation by measuring:

             1. Local and systemic vaccine-related clinical events.

             2. Physiological assessments: heart rate, temperature, blood pressure.

             3. Haematology (blood counts and ESR), biochemistry parameters.

        2. Metabolic, innate and adaptive immune responses including:

             1. Innate immune activation detected by global gene expression in whole blood

             2. Metabolic responses detected by metabolic gene expression and pathway activation in
                whole blood

             3. Adaptive immunity determined by:

           i. Humoral immune response via serum anti-influenza HAI titre

           ii. Cellular immune response via enumeration of HA-specific CD4+ T cells expressing
           activation markers and/or cytokines following in vitro stimulation and analysis by flow
           cytometry.

           d. Innate and adaptive immune activation detected by gene pathway activation in whole
           blood

           e. Immune activation detected by concentration of selected inflammatory soluble
           mediators in serum including:

           i. chemokines and cytokines

           ii. acute phase proteins

        3. Genetic testing of subjects when deemed necessary (genetic testing analysis may be SNIP
           analysis or full genome analysis).

        4. Correlations in changes in innate and adaptive 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 the investigators 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): Fluad; Saline
Intervention type(s): Biological; Biological
Intervention description(s): Randomized assignment; Randomized assignment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science