Evaluate the immune response and reactogenicity of H5N1 vaccination in adults aged 18 years and above (as part of a tetravalent vaccine)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
601
Tetravalent influenza vaccine (MF59-eTIV-H5N1)and placebo on day 1 followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1+V3.
Pandemic influenza vaccine plus placebo on day 1 followed 3-5 weeks later by tetravalent influenza vaccine (MF59-eTIV-H5N1), including serology blood draw at V1+V3.
Pandemic influenza vaccine plus seasonal influenza vaccine, 3-5 weeks later pandemic influenza vaccine , including serology blood draw at V1+V3.
ATRIUM Gesundheitszentrum;
Holzkirchen, Germany
International Medicine & Public Health Dept. of Infect. Diseases
Munich, Germany
To Demonstrate the Equivalence of Antibody Response Against A/H5N1 Strain Elicited by the Three Different Immunization Schedules on Day 43.
The antibody response was determined by SRH assay. Geometric mean areas (GMAs) and geometric mean ratios (GMRs) in the SRH assay were used to demonstrate the equivalence. The statistical analysis was done based on the GMRs.
Time frame: up to day 43
Number of Subjects (Subjects ≤ 60 Years) With Reported Local Reactions After First Vaccination
Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization. The table represents local reactions after first vaccination in each arm differently.
Time frame: Up to 7 days after 1st vaccination
Number of Subjects (Subjects ≤60 Years) With Reported Local Reactions After Second Vaccination
Local reactions were collected up to 7 days after 1st vaccinations. All subjects were instructed to complete a diary card to record local reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.
Time frame: Up to 7 days after 2nd vaccination
Number of Subjects (Subjects ≤ 60 Years) With Reported Systemic Reactions After 1st and 2nd Vaccinations.
Systemic reactions were collected upto 7 days after 1st and 2nd vaccinations. All subjects were instructed to complete a diary card to record systemic reactions starting on the day of vaccination (after 6 hours) and for each of the 6 days following each immunization.
Time frame: 7 days after 1st and 2nd vaccinations each
Percentages of Subjects Achieving Seroconversion/Significant Increase in Antibody Titre/ Area as Measured by SRH and (HI) and at Least 4 Fold Rise in Titres by Micro-neutralization (MN) Assay-H5N1 Strain
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Pandemic influenza vaccine plus placebo followed 3-5 weeks later by tetravalent influenza vaccine (MF59-eTIV-H5N1), including serology blood draw at V1, V2 and V3.
Pandemic influenza vaccine plus seasonal influenza vaccine followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1, V2 and V3.
Tetravalent influenza vaccine (MF59-eTIV-H5N1)plus placebo followed 3-5 weeks later by pandemic influenza vaccine, including serology blood draw at V1, V2 and V3.
Measurement of immunogenicity in terms of significant increase in antibody titer and Seroconversion. Significant increase in antibody titer is defined as at least a four-fold increase from non-negative pre-vaccination serum (≥ 10) for HI or a 50% increase in area for SRH. Seroconversion is defined as negative pre-vaccination serum / post-vaccination titer ≥40 for HI (area ≥25 mm2 for SRH)
Time frame: up to day 43
Percentages of Subjects Achieving HI/MN ≥ 1:40 and SRH Area ≥ 25^mm2
Measurement of immunogenicity in terms of percentage of subjects achieving a titre ≥ 40/area ≥ 25mm\^2 after immunization as determined by HI (Haemagglutination Inhibition), MN(Microneutralization) and SRH assay.
Time frame: Up to 43 days
Antibody Response Determined by HI and MN Assay.
Measurement of immunogenicity in terms of Geometric mean titers (GMTs) as determined by HI and MN assay.
Time frame: Up to 43 days
Percentages of B-cell Antibodies Against H5N1 and H1N1 After Each Vaccination.
The Cell Mediated Immunity (CMI) response was evaluated in a randomly selected subgroup of approximately 92 subjects from all the vaccine groups out of a total of 601 enrolled subjects. Frequency of circulating memory B cells (MBC), capable of differentiating in vitro into cell secreting IgG (Immunoglobulin G) antibodies specific for H5N1 (the subunit from A/Vietnam/1194/2004) or for H1N1 (the subunit from A/Solomon Island/3/2006) were determined by an ELISA-coupled limiting dilution assay.The frequency of H5N1-IgG MBC and H1N1-IgG MBC was expressed as percentages (%) of total IgG producing MBC.
Time frame: Three weeks after first vaccination (day 22) and three weeks after second vaccination (day 43)
Mean T-Cells Per Million Total Cells (95% CI) in Response to H5 Peptides and H5N1 Subunit
Frequency and functionality of vaccine antigen-specific CD4+ (cluster of differentiation 4) T cells was assessed in peripheral blood (PBMC) taken at days 1, 22 and 43 after in vitro stimulation with: Library of 70 peptides spanning the whole H5 A/Vietnam/1194/2004 protein (H5 pool of 70 Vietnam) H5N1 subunit from A/Vietnam/1194/2004 (H5N1 Vietnam) H3N2 subunit from A/ Wisconsin/67/2005 (H3N2 Wisconsin) H1N1 subunit from A/Solomon Islands/3/2006 (H1N1 Solomon Islands) Polyclonal stimulus agonistic aCD3 mAb \[monoclonal antibody (aCD3)\]. The change in frequency of T-cells was measured.
Time frame: Three weeks after 1st vaccination (day 22) and three weeks after 2nd vaccination (day 43)