A randomized, triple-blinded, placebo-controlled, parallel group study, to assess the effect of multistrain probiotic on the immune response to the Influenza vaccination
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
120
Multistrain Probiotic
Placebo
Leof. Mesogeion 264,
Athens, Cholargos, Greece
Change in serum strain-specific geometric mean antibody titers (determined by hemagglutination inhibition [HAI] tests)
Change in serum strain-specific geometric mean antibody titers (determined by hemagglutination inhibition \[HAI\] tests) specific for each of the 3 (out of the 4) virus strains included in the INFLUVAC TETRA vaccine, between intervention and placebo from V2 to V3. Higher values mean better immune response.
Time frame: V2 (3 weeks), V3 (6 weeks)
Change in seroprotection rate (as measured by HAI tests)
Change in seroprotection rate (as measured by HAI tests) between verum and placebo groups for each of 3 (out of the 4) virus strains included in the INFLUVAC TETRA vaccine from V2 to V3. Seroprotection is defined as the proportion (percentage) of volunteers achieving an influenza antibody titer ≥1:40 by the HAI test. Higher values mean better immune response.
Time frame: V2 (3 weeks), V3 (6 weeks)
Change in seroconversion rate (as measured by HAI tests)
Change in seroconversion rate (as measured by HAI tests) between verum and placebo groups for each of 3 (out of the 4) virus strains included in the INFLUVAC TETRA vaccine from V2 to V3. Seroconversion is defined as the proportion of subjects with a pre-vaccination HAI titer \<1:10 and a post-vaccination HAI titer ≥1:40 or subjects with a pre-vaccination HAI titer \>1:10 and at least a 4-fold increase at day 42. Higher values mean better immune response.
Time frame: V2 (3 weeks), V3 (6 weeks)
Change in geometric mean neutralizing antibody (nAb) titers (as measured by microneutralization assays)
Change in geometric mean neutralizing antibody (nAb) titers specific for each of 3 (out of the 4) virus strains included in the INFLUVAC TETRA vaccine , as measured by a microneutralization assay from V2 to V3. Higher values mean better immune response.
Time frame: V2 (3 weeks), V3 (6 weeks)
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Change in seroprotection rate (as measured by nAb titers in a microneutralization assay)
Change in seroprotection rate (as measured by nAb titers) specific for each of 3 (out of the 4) virus strains included in the INFLUVAC TETRA vaccine, as measured by a microneutralization assay from V2 to V3. Seroprotection is defined as the proportion (percentage) of volunteers achieving an influenza nAb titer ≥1:40 in MN test. Higher values mean better immune response.
Time frame: V2 (3 weeks), V3 (6 weeks)
Change in seroconversion rate (as measured by nAb titers in a microneutralization assay)
Change in seroconversion rate (as measured by nAb titers) specific for each of 3 (out of the 4) virus strains included in the INFLUVAC TETRA vaccine, as measured by a microneutralization assay from V2 to V3. Seroconversion is defined as the proportion of subjects with a pre-vaccination nAb titer \<1:10 and a post-vaccination nAb titer ≥1:40 or subjects with a pre-vaccination MN titer \>1:10 and at least a 4-fold increase at day 42. Higher values mean better immune response.
Time frame: V2 (3 weeks), V3 (6 weeks)
Change in the adaptive immune response
Change in the adaptive immune response, assessed by change in total plasma, strain A and B specific IgA, IgM, IgG from V2 to V3 between intervention and placebo. Higher values mean better immune response.
Time frame: V2 (3 weeks), V3 (6 weeks)
Change in innate immune response
Change in innate immune responses assessed by difference in plasma concentrations of interferon-gamma, TNF-alpha, IL-2, IL-10 from V2 to V3 between intervention and placebo. Higher values mean better immune response.
Time frame: V2 (3 weeks), V3 (6 weeks)
VAPI (Vaccinees' Perception of Injection) Questionnaire
VAPI (Vaccinees' Perception of Injection) Questionnaire difference at V3 between intervention and placebo. Higher values mean worse perception of the vaccine.
Time frame: V3 (6 weeks)
Change in GSRS (Gastrointestinal Symptom Rating Scale) questionnaire scoring
Change in GSRS (Gastrointestinal Symptom Rating Scale) questionnaire scoring from baseline to V2,V2 to V3 and baseline to V3 between intervention and placebo. Higher values mean more troublesome symptoms
Time frame: V1 (Baseline), V2 (3 weeks), V3 (6 weeks)
Change in stool microbiome composition
Change in stool microbiome composition between verum and placebo between V1 and V3 in 40% of the cohort (40% of each study arm).
Time frame: V1 (Baseline), V3 (6 weeks)
Adverse Events
The number of adverse events (AE)/serious adverse events (SAE) (related to the study IP) occurring during the study compared to placebo.
Time frame: V3 (6 weeks)