Vaccine Responsiveness During Allergy De-sensitization Treatment, Vaccine Responsiveness in Allergy
Conditions
Brief summary
Allergic patients especially those undergoing de-sensitization treatment have an altered immune responsiveness. The investigators aim to find out whether this influences immune responses to primary and booster vaccinations.
Detailed description
Allergic patients generally have an altered immunologic profile (Th2 bias), and allergic individuals undergoing de-sensitization treatment display an increased production of immune suppressive cytokines. The investigators measure humoral and cellular immune responses to routine vaccination (Tick-borne Encephalitis \[TBE\] booster) in allergic patients with and without de-sensitization treatment to determine whether allergy negatively influences vaccine induced immune responses and protection.
Interventions
BIOLOGICALTBE booster vaccination
Sponsors
Medical University of Vienna
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* completed primary TBE immunization + at least one booster immunization * adults of both sexes between 18 and 60 years of age * willingness to sign written informed consent form
Exclusion criteria
* age \< 18 and \> 60 years * prior TBE infection * Hepatitis A vaccination * pregnancy and breast feeding * acute infection on day of inclusion (day 0), body temperature \>37,9°C * concomitant medications: systemic cortisone therapy, chemotherapy, immunosuppressive therapy 4 weeks prior to or during study * administration of other vaccines 4 weeks before/after TBE vaccination * planned surgery within 2 weeks before/after TBE vaccination * Start of de-sensitization and the first 4 weeks of allergen dose escalation * any contraindication to administration of FSME-Immun® vaccine according to manufacturer's instructions * history of malignant disease within the last 5 years * autoimmune diseases * drug addictions * plasma donors * receipt of blood transfusions or immuno globulins within 3 month before study entry
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Humoral TBE Immunity | one month after booster vaccination | Geometric mean titers of TBE specific neutralizing Abs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cellular Immune Response - Cytokine Production | before (day 0) and 1week after booster vaccination | cytokine production of antigen-specifically re-stimulated PMBC, IL-2 (interleukin 2) IFN g (interferon gamma) IL-10 (interleukin 10) IL-5 (interleukin 5) |
| Cellular Immune Response - Lymphocyte Subpopulations | before (day 0) and 1week after booster vaccination | analyses of naive, memory and regulatory sub-populations of B- and T-lymphocytes |
| TBE Titer Course | before (day 0) until 6 months after booster vaccination | Fold Change in TBE Specific Neutralizing Antibodies from day 0 (before booster) and one week, one month and 6 months after booster vaccination |
Countries
Austria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Allergic Patients Allergic patients receive TBE booster vaccination | 49 |
| Allergic Patients With De-sensitization Treatment Allergic patients with de-sensitization treatment receive TBE booster vaccination | 21 |
| Healthy Controls Healthy controls receive TBE booster vaccination | 49 |
| Total | 119 |
Baseline characteristics
| Characteristic | Allergic Patients | Allergic Patients With De-sensitization Treatment | Healthy Controls | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants | 21 Participants | 49 Participants | 119 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 49 Participants | 21 Participants | 49 Participants | 119 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Austria | 49 participants | 21 participants | 49 participants | 119 participants |
| Sex: Female, Male Female | 30 Participants | 12 Participants | 30 Participants | 72 Participants |
| Sex: Female, Male Male | 19 Participants | 9 Participants | 19 Participants | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 21 | 0 / 49 |
| other Total, other adverse events | 23 / 49 | 12 / 21 | 27 / 49 |
| serious Total, serious adverse events | 0 / 49 | 0 / 21 | 0 / 49 |
Outcome results
Primary
Humoral TBE Immunity
Geometric mean titers of TBE specific neutralizing Abs
Time frame: one month after booster vaccination
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Allergic Patients | Humoral TBE Immunity | 317.90 titer |
| Allergic Patients With De-sensitization Treatment | Humoral TBE Immunity | 250.10 titer |
| Healthy Controls | Humoral TBE Immunity | 282.20 titer |
Secondary
Cellular Immune Response - Cytokine Production
cytokine production of antigen-specifically re-stimulated PMBC, IL-2 (interleukin 2) IFN g (interferon gamma) IL-10 (interleukin 10) IL-5 (interleukin 5)
Time frame: before (day 0) and 1week after booster vaccination
Population: the missing cytokine concentrations were not used for calculation because of invalid positive controls (due to poor PBMC \[peripheral blood mononuclear cell\] viability)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Allergic Patients | Cellular Immune Response - Cytokine Production | IFNg before vaccination | 37.85 pg/ml |
| Allergic Patients | Cellular Immune Response - Cytokine Production | IFNg 1 week post vacc | 54.19 pg/ml |
| Allergic Patients | Cellular Immune Response - Cytokine Production | IL-10 before vaccination | 35.21 pg/ml |
| Allergic Patients | Cellular Immune Response - Cytokine Production | IL-10 one week post vacc | 48.90 pg/ml |
| Allergic Patients | Cellular Immune Response - Cytokine Production | IL-2 before vaccination | 52.62 pg/ml |
| Allergic Patients | Cellular Immune Response - Cytokine Production | IL-2 one week post vacc | 53.80 pg/ml |
| Allergic Patients | Cellular Immune Response - Cytokine Production | IL-5 before vaccination | 2.08 pg/ml |
| Allergic Patients | Cellular Immune Response - Cytokine Production | IL-5 one week post vaccination | 2.96 pg/ml |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Cytokine Production | IL-10 before vaccination | 38.86 pg/ml |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Cytokine Production | IL-5 before vaccination | 1.85 pg/ml |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Cytokine Production | IL-10 one week post vacc | 52.13 pg/ml |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Cytokine Production | IL-2 before vaccination | 35.41 pg/ml |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Cytokine Production | IL-2 one week post vacc | 37.11 pg/ml |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Cytokine Production | IFNg before vaccination | 42.54 pg/ml |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Cytokine Production | IFNg 1 week post vacc | 59.45 pg/ml |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Cytokine Production | IL-5 one week post vaccination | 1.87 pg/ml |
| Healthy Controls | Cellular Immune Response - Cytokine Production | IL-10 before vaccination | 30.28 pg/ml |
| Healthy Controls | Cellular Immune Response - Cytokine Production | IFNg 1 week post vacc | 77.27 pg/ml |
| Healthy Controls | Cellular Immune Response - Cytokine Production | IFNg before vaccination | 38.91 pg/ml |
| Healthy Controls | Cellular Immune Response - Cytokine Production | IL-10 one week post vacc | 52.28 pg/ml |
| Healthy Controls | Cellular Immune Response - Cytokine Production | IL-5 before vaccination | 2.04 pg/ml |
| Healthy Controls | Cellular Immune Response - Cytokine Production | IL-2 one week post vacc | 51.07 pg/ml |
| Healthy Controls | Cellular Immune Response - Cytokine Production | IL-2 before vaccination | 37.20 pg/ml |
| Healthy Controls | Cellular Immune Response - Cytokine Production | IL-5 one week post vaccination | 2.85 pg/ml |
Secondary
Cellular Immune Response - Lymphocyte Subpopulations
analyses of naive, memory and regulatory sub-populations of B- and T-lymphocytes
Time frame: before (day 0) and 1week after booster vaccination
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Allergic Patients | Cellular Immune Response - Lymphocyte Subpopulations | B cells (CD19 +) at day 0 | 7.63 percent of total lymphocytes |
| Allergic Patients | Cellular Immune Response - Lymphocyte Subpopulations | cytotoxic T cells (CD8 +) 1 week after booster | 20.9 percent of total lymphocytes |
| Allergic Patients | Cellular Immune Response - Lymphocyte Subpopulations | Tregs (CD4+ FOXP3+) at day 0 | 4.65 percent of total lymphocytes |
| Allergic Patients | Cellular Immune Response - Lymphocyte Subpopulations | T cells (CD3 +) at day 0 | 69.3 percent of total lymphocytes |
| Allergic Patients | Cellular Immune Response - Lymphocyte Subpopulations | Tregs (CD4+ FOXP3+) 1 week after booster | 4.54 percent of total lymphocytes |
| Allergic Patients | Cellular Immune Response - Lymphocyte Subpopulations | B cells (CD19 +) 1 week after booster vaccination | 7.22 percent of total lymphocytes |
| Allergic Patients | Cellular Immune Response - Lymphocyte Subpopulations | T cells (CD3 +) 1 week after booster vaccination | 68.7 percent of total lymphocytes |
| Allergic Patients | Cellular Immune Response - Lymphocyte Subpopulations | T helper cells (CD4 +) at day 0 | 42.3 percent of total lymphocytes |
| Allergic Patients | Cellular Immune Response - Lymphocyte Subpopulations | T helper cells (CD4 +) 1 week after booster | 42.7 percent of total lymphocytes |
| Allergic Patients | Cellular Immune Response - Lymphocyte Subpopulations | cytotoxic T cells (CD8 +) at day 0 | 21.5 percent of total lymphocytes |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Lymphocyte Subpopulations | T cells (CD3 +) 1 week after booster vaccination | 74.7 percent of total lymphocytes |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Lymphocyte Subpopulations | B cells (CD19 +) 1 week after booster vaccination | 6.34 percent of total lymphocytes |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Lymphocyte Subpopulations | cytotoxic T cells (CD8 +) 1 week after booster | 20.7 percent of total lymphocytes |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Lymphocyte Subpopulations | B cells (CD19 +) at day 0 | 7.01 percent of total lymphocytes |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Lymphocyte Subpopulations | cytotoxic T cells (CD8 +) at day 0 | 20.3 percent of total lymphocytes |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Lymphocyte Subpopulations | Tregs (CD4+ FOXP3+) at day 0 | 5.36 percent of total lymphocytes |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Lymphocyte Subpopulations | T cells (CD3 +) at day 0 | 73.7 percent of total lymphocytes |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Lymphocyte Subpopulations | T helper cells (CD4 +) at day 0 | 49.1 percent of total lymphocytes |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Lymphocyte Subpopulations | Tregs (CD4+ FOXP3+) 1 week after booster | 5.60 percent of total lymphocytes |
| Allergic Patients With De-sensitization Treatment | Cellular Immune Response - Lymphocyte Subpopulations | T helper cells (CD4 +) 1 week after booster | 50.5 percent of total lymphocytes |
| Healthy Controls | Cellular Immune Response - Lymphocyte Subpopulations | Tregs (CD4+ FOXP3+) 1 week after booster | 4.21 percent of total lymphocytes |
| Healthy Controls | Cellular Immune Response - Lymphocyte Subpopulations | T cells (CD3 +) at day 0 | 68.2 percent of total lymphocytes |
| Healthy Controls | Cellular Immune Response - Lymphocyte Subpopulations | T cells (CD3 +) 1 week after booster vaccination | 70.6 percent of total lymphocytes |
| Healthy Controls | Cellular Immune Response - Lymphocyte Subpopulations | B cells (CD19 +) at day 0 | 7.11 percent of total lymphocytes |
| Healthy Controls | Cellular Immune Response - Lymphocyte Subpopulations | B cells (CD19 +) 1 week after booster vaccination | 6.39 percent of total lymphocytes |
| Healthy Controls | Cellular Immune Response - Lymphocyte Subpopulations | T helper cells (CD4 +) at day 0 | 41.6 percent of total lymphocytes |
| Healthy Controls | Cellular Immune Response - Lymphocyte Subpopulations | T helper cells (CD4 +) 1 week after booster | 43.0 percent of total lymphocytes |
| Healthy Controls | Cellular Immune Response - Lymphocyte Subpopulations | cytotoxic T cells (CD8 +) at day 0 | 20.6 percent of total lymphocytes |
| Healthy Controls | Cellular Immune Response - Lymphocyte Subpopulations | cytotoxic T cells (CD8 +) 1 week after booster | 21.2 percent of total lymphocytes |
| Healthy Controls | Cellular Immune Response - Lymphocyte Subpopulations | Tregs (CD4+ FOXP3+) at day 0 | 4.49 percent of total lymphocytes |
Secondary
TBE Titer Course
Fold Change in TBE Specific Neutralizing Antibodies from day 0 (before booster) and one week, one month and 6 months after booster vaccination
Time frame: before (day 0) until 6 months after booster vaccination
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Allergic Patients | TBE Titer Course | fold change 4 weeks after booster | 3.02 fold change from d0 (before booster) |
| Allergic Patients | TBE Titer Course | fold change 1 week after booster | 1.46 fold change from d0 (before booster) |
| Allergic Patients | TBE Titer Course | fold change 6 month after booster | 1.95 fold change from d0 (before booster) |
| Allergic Patients With De-sensitization Treatment | TBE Titer Course | fold change 4 weeks after booster | 3.01 fold change from d0 (before booster) |
| Allergic Patients With De-sensitization Treatment | TBE Titer Course | fold change 1 week after booster | 1.80 fold change from d0 (before booster) |
| Allergic Patients With De-sensitization Treatment | TBE Titer Course | fold change 6 month after booster | 2.53 fold change from d0 (before booster) |
| Healthy Controls | TBE Titer Course | fold change 1 week after booster | 1.79 fold change from d0 (before booster) |
| Healthy Controls | TBE Titer Course | fold change 6 month after booster | 1.79 fold change from d0 (before booster) |
| Healthy Controls | TBE Titer Course | fold change 4 weeks after booster | 2.56 fold change from d0 (before booster) |