Safety Markers of Adjuvanted Influenza Vaccine Clinical Trial
Official title:
Clinical Study to Generate a Set of Data Characterising Clinical Events, Physiological Responses, and Innate and Adaptive Immune Responses Following a Single IM Immunisation With Fluad Seasonal Influenza Vaccine or Placebo in Healthy Adults
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.
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. ;