This clinical fase IV study, using the administration of a single dose of a quadrivalent, inactivated, split influenza virus vaccine as biological intervention will mirror a study conducted at Imperial College, London, UK that will use a challenge with live virus as intervention. Comparison of the clinical observations and laboratory measurements generated in both studies will inform us about the similarities and differences in innate and adaptive immune responses elicited by both types of exposure to influenza virus antigen(s).
The study is a monocentric, open label study. All subjects will receive a single dose of alfa-Rix Tetra 2016-2017. The following will be measured - clinical events (recorded adverse events), physiological responses (heart rate, blood pressure, temperature, injection site), innate immune responses (cytokine levels and whole blood gene expression) and adaptive immune responses (serum antibody and antigen-specific cellular responses) at various time points after immunisation. At each study visit, full physiological parameters (including body temperature, heart rate, blood pressure) will be obtained and the injection site will be examined for the presence of any redness or swelling that will be measured and recorded. Standardized diary cards will be used to collect solicited and unsolicited clinical event data. At each visit the diary cards will be examined and any relevant clinical event will be entered into the clinical event form. Participants will be asked to monitor oral temperature from day 0 until day 7 when they wake up and when going to bed. The results of these measurements will be reported in a diary card. Any skin reactions at the site of injection will be evaluated; largest diameter of redness and swelling will be measured with a ruler and data reported on the diary card. Samples of blood (PAXgene tubes, plasma, serum and PBMCs (peripheral blood mononuclear cells)) will be collected for analysis and processing using protocols already in place. Subjects will also have blood obtained for standard safety markers (haematology, biochemistry) as well as acute phase proteins. 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, body temperature, blood pressure. 3. Haematology (Complete Blood Count (CBC), Erythrocyte Sedimentation Rate (ESR) , phenotyping of White Blood Cells (WBC)), biochemistry parameters. 2. Innate and adaptive immune responses including: 1. Innate immune activation detected by global gene expression in whole blood 2. Adaptive immunity determined by: i. Humoral immune response via serum anti-influenza HAI (Haemagglutination Inhibition) titre ii. Cellular immune response c. 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 (Single Nucleotide Polymorphism) analysis or full genome analysis). 4. Correlations in changes in innate and adaptive immune activation with adverse events, haematology and biochemistry panels, genotype and physiological assessments The study team will biobank all samples for the duration of the BIOVACSAFE programme so that different samples and different time points depending on the results generated can selectively be analysed, principally from the gene expression analysis of whole blood.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
20
1 dose to be administered on Day 0, the first visit
University Hospital - 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
Severity 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 time of vaccination up to 28 days after vaccination
Frequency of systemic vaccine-related clinical events.
Participants will report these events on a diary, scoring the events from 0 (absent) to 3 (severe)
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
Severity of systemic vaccine-related clinical events.
Participants will report these events on a diary, scoring the events from 0 (absent) to 3 (severe)
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in pulse.
Will be measured during the study visits
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in body temperature
Will be measured during the study visits
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in blood pressure
Will be measured during the study visits
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in haematology (CBC, ESR, phenotyping of WBC) parameters
blood will be collected during the study visits
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in biochemistry parameters
blood will be collected during the study visits
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in global gene expression measured on whole blood samples
blood will be collected during the study visits
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in serum HAI titre in serum samples
blood will be collected during the study visits
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
Change from pre-immunisation values of adaptive cellular immune response via enumeration of influenza-specific CD4+ T cells expressing activation markers and/or cytokines following in vitro stimulation and analysis by flow cytometry
blood will be collected during the study visits
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in concentration of selected cytokines and acute phase proteins in serum samples
blood will be collected during the study visits
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
Change from pre-immunisation baseline values in PBMC cytokine secretion, proliferation or surface markers in response to in vitro stimulation with influenza antigens
blood will be collected during the study visits
Time frame: At selected timepoints from time of vaccination up to 28 days after vaccination
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