CompletedNCT02511535Updated Oct 25, 2019Results posted

TBE (Tick-borne Encephalitis) Vaccination in Allergic Patients

A Phase 4 interventional study of TBE booster vaccination in Vaccine Responsiveness in Allergy and Vaccine Responsiveness During Allergy De-sensitization Treatment, sponsored by Medical University of Vienna. Completed at 1 site in Austria. Open to participants aged 18 Years to 60 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-10-25.

Sponsored by Medical University of Vienna · Phase 4, Interventional, and Prevention

Phase: Phase 4
Study type: Interventional
Enrollment: 119
Allocation: Non-randomized
Ages: 18 Years to 60 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Vaccine Responsiveness in Allergy
Vaccine Responsiveness During Allergy De-sensitization Treatment

Browse trials for

Who can participate

Ages eligible: 18 Years to 60 Years
Sexes eligible: All
Accepts 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

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

Study design

Phase: Phase 4
Primary purpose: Prevention
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 119 participants (actual)

Study arms

Experimental
Allergic patients
Allergic patients receive TBE booster vaccination
Biological: TBE booster vaccination
Experimental
Allergic patients with de-sensitization treatment
Allergic patients with de-sensitization treatment receive TBE booster vaccination
Biological: TBE booster vaccination
Active comparator
Healthy controls
Healthy controls receive TBE booster vaccination
Biological: TBE booster vaccination

Interventions

BiologicalTBE booster vaccination
Also known as: Vaccine: FSME-Immun® (Fruehsommer-Meningoencephalitis), One dose (0.5 ml) contains:, 2.4 micrograms Tick-Borne Encephalitis Virus ( strain Neudoerfl),, adsorbed on aluminium oxide, hydrated (0.35 milligrams Al3+), Manufacturer: Baxter Innovations GmbH

What researchers measure

Primary outcomes

Humoral TBE Immunity
Geometric mean titers of TBE specific neutralizing Abs
Time frame: one month after booster vaccination

Secondary outcomes

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
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
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

Results

Posted Oct 25, 2019

Participant flow

Participant flow — Overall Study
Milestone	Allergic Patients	Allergic Patients With De-sensitization Treatment	Healthy Controls
Started	49	21	49
Completed	49	21	49
Not completed	0	0	0

Outcome measures

PrimaryHumoral TBE Immunity

Geometric mean titers of TBE specific neutralizing Abs

Time frame:: one month after booster vaccination
Reported as:: Geometric mean · titer

Humoral TBE Immunity
titer	Allergic Patients	Allergic Patients With De-sensitization Treatment	Healthy Controls
Humoral TBE Immunity	317.90 (238.70 to 423.30)	250.10 (143.90 to 434.40)	282.20 (210.60 to 378.20)

SecondaryCellular 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
Reported as:: Geometric mean · pg/ml

Cellular Immune Response - Cytokine Production
pg/ml	Allergic Patients	Allergic Patients With De-sensitization Treatment	Healthy Controls
IFNg before vaccination	37.85 (25.86 to 55.39)	42.54 (23.36 to 77.49)	38.91 (25.13 to 59.01)
IFNg 1 week post vacc	54.19 (37.61 to 78.08)	59.45 (32.67 to 108.17)	77.27 (52.26 to 114.25)
IL-10 before vaccination	35.21 (25.90 to 47.86)	38.86 (23.75 to 63.58)	30.28 (21.15 to 43.37)
IL-10 one week post vacc	48.90 (36.60 to 65.33)	52.13 (37.00 to 73.44)	52.28 (36.47 to 74.95)
IL-2 before vaccination	52.62 (36.54 to 75.78)	35.41 (21.25 to 59.02)	37.20 (24.43 to 56.64)
IL-2 one week post vacc	53.80 (37.03 to 78.18)	37.11 (24.44 to 56.34)	51.07 (34.57 to 75.44)
IL-5 before vaccination	2.08 (1.81 to 2.40)	1.85 (1.85 to 1.85)	2.04 (1.87 to 2.23)
IL-5 one week post vaccination	2.96 (2.32 to 3.77)	1.87 (1.84 to 1.90)	2.85 (2.23 to 3.64)

SecondaryCellular 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
Reported as:: Mean · percent of total lymphocytes

Cellular Immune Response - Lymphocyte Subpopulations
percent of total lymphocytes	Allergic Patients	Allergic Patients With De-sensitization Treatment	Healthy Controls
T cells (CD3 +) at day 0	69.3 (66.9 to 71.8)	73.7 (70.9 to 76.5)	68.2 (65.5 to 71.0)
T cells (CD3 +) 1 week after booster vaccination	68.7 (66.1 to 71.2)	74.7 (72.4 to 77.1)	70.6 (68.3 to 72.9)
B cells (CD19 +) at day 0	7.63 (6.67 to 8.57)	7.01 (6.04 to 7.98)	7.11 (6.34 to 7.89)
B cells (CD19 +) 1 week after booster vaccination	7.22 (6.33 to 8.11)	6.34 (5.34 to 7.34)	6.39 (5.78 to 7.01)
T helper cells (CD4 +) at day 0	42.3 (39.9 to 44.6)	49.1 (45.5 to 52.4)	41.6 (38.7 to 44.4)
T helper cells (CD4 +) 1 week after booster	42.7 (40.4 to 45.0)	50.5 (47.6 to 53.4)	43.0 (40.1 to 45.8)
cytotoxic T cells (CD8 +) at day 0	21.5 (19.8 to 23.3)	20.3 (17.0 to 23.4)	20.6 (18.4 to 22.8)
cytotoxic T cells (CD8 +) 1 week after booster	20.9 (19.3 to 22.6)	20.7 (17.5 to 23.8)	21.2 (19.0 to 23.3)
Tregs (CD4+ FOXP3+) at day 0	4.65 (4.20 to 5.13)	5.36 (4.61 to 6.16)	4.49 (4.10 to 4.89)
Tregs (CD4+ FOXP3+) 1 week after booster	4.54 (4.10 to 5.01)	5.60 (4.93 to 6.30)	4.21 (3.84 to 4.60)

SecondaryTBE 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
Reported as:: Mean · fold change from d0 (before booster)

TBE Titer Course
fold change from d0 (before booster)	Allergic Patients	Allergic Patients With De-sensitization Treatment	Healthy Controls
fold change 1 week after booster	1.46 (1.23 to 1.73)	1.80 (1.36 to 2.37)	1.79 (1.50 to 2.14)
fold change 4 weeks after booster	3.02 (2.43 to 3.77)	3.01 (2.05 to 4.41)	2.56 (2.09 to 3.13)
fold change 6 month after booster	1.95 (1.54 to 2.46)	2.53 (1.81 to 3.54)	1.79 (1.41 to 2.29)

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Allergic Patients	0/49 (0%)	0/49 (0%)	23/49 (46.9%)
Allergic Patients With De-sensitization Treatment	0/21 (0%)	0/21 (0%)	12/21 (57.1%)
Healthy Controls	0/49 (0%)	0/49 (0%)	27/49 (55.1%)

Most frequent other events

Most frequent other events
Event	Allergic Patients	Allergic Patients With De-sensitization Treatment	Healthy Controls
vaccine reactogenicitySkin and subcutaneous tissue disorders	23/49	12/21	27/49

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Allergic Patients	Allergic Patients With De-sensitization Treatment	Healthy Controls	Total
<=18 years	0	0	0	0
Between 18 and 65 years	49	21	49	119
>=65 years	0	0	0	0

Sex: Female, Male
Sex: Female, Male(Participants)	Allergic Patients	Allergic Patients With De-sensitization Treatment	Healthy Controls	Total
Female	30	12	30	72
Male	19	9	19	47

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Allergic Patients	Allergic Patients With De-sensitization Treatment	Healthy Controls	Total
Hispanic or Latino	0	0	0	0
Not Hispanic or Latino	49	21	49	119
Unknown or Not Reported	0	0	0	0

Region of Enrollment
Region of Enrollment(participants)	Allergic Patients	Allergic Patients With De-sensitization Treatment	Healthy Controls	Total
Austria	49	21	49	119

Study locations

1 site

Medical University Vienna, Institute of Specific Prophylaxis and Tropical Medicine
Vienna, 1090, Austria

References and documents

Publications

Garner-Spitzer E, Seidl-Friedrich C, Zwazl I, Hofer M, Kinaciyan T, Jarisch R, Stiasny K, Zlabinger GJ, Kundi M, Wiedermann U. Allergic patients with and without allergen-specific immunotherapy mount protective immune responses to tick-borne encephalitis vaccination in absence of enhanced side effects or propagation of their Th2 bias. Vaccine. 2018 May 11;36(20):2816-2824. doi: 10.1016/j.vaccine.2018.03.076. Epub 2018 Apr 16. PubMed 29673942 ↗

Registry details

Key details

Study ID: NCT02511535
Lead sponsor: Medical University of Vienna
Responsible party: Univ. Prof. Dr. Ursula Wiedermann (Univ.-Prof. Dr. Ursula Wiedermann, MD, PhD, Medical University of Vienna) — Principal investigator
First posted: Jul 30, 2015
Start date: Sep 2013
Primary completion: Feb 2016
Completion: Sep 2016
Results posted: Oct 25, 2019
Last update: Oct 25, 2019

Study contacts

Ursula Wiedermann, MD, PhD

principal investigator · Medical University Vienna

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2019. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Encephalitis, Tick-Borne→

Other studies from this sponsor

Medical University of Vienna

Start the discussion