Influenza virus infection MedDRA version: 16.1 Level: HLT Classification code 10022005 Term: Influenza viral infections System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Bacille Calmette Guérin vaccination
Product Name: Bacille Calmette Guérin vaccination
Product Code: RVG 17661
Pharmaceutical Form: Powder and solution for solution for injection
Pharmaceut
Sponsors
Radboud University Nijmegen Medical Centre
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: - Age =18 and =35 yrs or =65 yrs - Male - Healthy Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: - Prior exposure to ‘Influvac’ influenza virus strains , measured by antibody titres. Previous exposure is defined by antibody titres =1:40. - History of influenza vaccination within the year prior to study entry - History of BCG vaccination within 5 years prior to study entry - History of Mantoux testing within the year prior to study entry - Vaccination other than BCG or influenza, within 3 months prior to study or within study period - Medical history of any disease associated with immune deficiency - Clinically significant acute illness, including infections, within 4 weeks before vaccination - Participation in a drug trial or donation of blood 3 months prior to study entry - Use of recreational drugs within 21 days prior to experiment day - Recent hospital admission or surgery with general anaesthesia (<3 months) - Known chronic kidney or liver disease - Latent or active tuberculosis infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the effects of BCG-vaccination on the immune response induced by subsequent influenza vaccination in healthy volunteers. This will be determined by measuring the Th1/Th2 response, and antibody titers induced by influenza vaccination in seronegative healthy volunteers who are, prior to influenza vaccination, vaccinated with either BCG or placebo in a double-blind randomized manner. ;Secondary Objective: There are 6 secondary objectives: 1. To determine the effects of BCG-vaccination on ex vivo responsiveness of leukocytes to inactivated influenza virus before and after influenza vaccination. 2. To determine the effects of BCG-vaccination on ex vivo responsiveness of leukocytes to various not related inflammatory stimuli following influenza vaccination. 3. To determine the effects of BCG-vaccination on the phenotype of circulating leukocytes following influenza vaccination (e.g. expression pattern of cell-surface receptors by use of flow cytometry). 4. To determine the effects of BCG-vaccination on inflammatory transcriptional pathways (determined by qPCR/microarrays) following influenza vaccination. 5. To determine the effects of BCG-vaccination on epigenetic changes, including H3K4 trimethylation, in circulating immune cells following influenza vaccination. 6. To determine whether age influences the immune modulating effects of BCG-vaccination. ;Primary end point(s): The primary study endpoint is the difference in influenza antibody titres 2 and 4 weeks (±2 days) after influenza vaccination between BCG-vaccinated subjects and subjects in the control group.;Timepoint(s) of evaluation of this end point: 2 and 4 weeks (±2 days) after influenza vaccination | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Proportion of participants in each group who achieved seroprotection (defined by antibody titre =1:40), 1, 2, 3 and 4 weeks (±2 days) after influenza vaccination. - Proportion of participants in each group who achieved seroconversion (defined by a =4-fold rise in antibody titre), 1, 2, 3 and 4 weeks ((±2 days) after influenza vaccination. - IFN-gamma/IL-10 production (reflecting the Th1/Th2 immune response) of leukocytes ex vivo stimulated with inactivated influenza virus (0.1ug HA/ml), before BCG vaccination, before influenza vaccination, and 2 and 4 weeks after influenza vaccination. - Production of Type 1 IFNs, IL-17 and IL-22 by leukocytes ex vivo stimulated with inactivated influenza virus (0.1ug HA/ml), before BCG vaccination, before influenza vaccination, and 2 and 4 weeks after influenza vaccination. - Production of other inflammatory mediators (including TNFa, IL-1ß, IFN-gamma, IL-10, IL-17, IL-22) by leukocytes ex vivo stimulated with m. tuberculosis (1ug/ml end protein concentration), s. aureus (1x10e6 microorganisms/ml), C. albicans (1x10e6 microorgansims/ml strain UC820), and inactivated influenza ( 0.1ug HA/ml) , before BCG vaccination, before influenza vaccination, and 2 and 4 weeks after influenza vaccination. - The phenotype of circulating leukocytes (expression of surface markers, including, but not limited to CD45, CD3, CD4, CD8, CD56, CD14, CD11b, TLR4, TLR2), before BCG vaccination, before influenza vaccination, and 2 and 4 weeks after influenza vaccination. - Inflammatory transcriptional pathways (by use of qPCR/microarrays) , before BCG vaccination, before influenza vaccination, and 2 and 4 weeks after influenza vaccination. - Epigenetic changes in leukocytes, including H3K4 trimethylation, before BCG vaccination, before influenza vaccination, and 4 weeks after influenza vaccination. - Subanalyses will include differences in all these parameters between young and older subjects. ;Timepoint(s) of evaluation | — |
Countries
Netherlands
Contacts
Public ContactJenneke Leentjens
Radboud University Nijmegen Medical Centre
Outcome results
None listed