Clinical trial NCT05921448: Vaccine Pandemic Preparedness Through Airway Immunology Characterization
Official title: In-depth Immunological Analysis of Airway Immunity Following Nasal Live Attenuated and Intramuscular Influenza Vaccine
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Influenza, Human
Lead sponsor: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
Sponsor class: OTHER
Collaborators: name: The Novo Nordic Foundation
First posted: 2023-06-27
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 49
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2-arm randomized, placebo-controlled, multicenter, parallel group intervention study in patients aged between 18-49.

Participants will be randomly allocated to one of four treatment groups.

Conducted in adherence with Good Clinical Practice (GCP).
Primary purpose: PREVENTION

Brief summary: The study aims to compare the effectiveness of live attenuated influenza vaccines (LAIV) and intramuscular-inactivated vaccines (IIV) in healthy individuals aged 18-49. It will investigate cellular and humoral responses, identify immunological markers for targeted vaccine improvement, and establish a collaborative platform for accelerated immunological and clinical vaccine research.

Detailed description: There are several types of vaccines and the focus on the important role of vaccines in health has increased after the SARS-CoV-2 pandemic. Therefore, it is desired to investigate whether so-called 'live attenuated influenza vaccines' (LAIV) can prove more effective than the most frequently used 'intramuscular-inactivated vaccines' (IIV).

Several studies have previously compared the humoral and cellular response to LAIV and IIV and some of these have shown that LAIV elicits a more robust cellular response than intramuscularly administered vaccines.

In the study, the immunological differences in cellular and humoral response following vaccination either intramuscularly or nasally will be characterized. The patient group will consist of healthy individuals between 18-49 years of age. It is further desired to identify immunological markers that vaccines can be directed against in order to improve the immunological response. Finally, a platform for collaboration on accelerated immunological and clinical vaccine research will be established.

The study is a randomized, double-blind, placebo-controlled study. It is carried out in several locations and is Good Clinical Practice monitored.

Eligibility criteria: Inclusion Criteria:

1. Healthy individuals (Charlson´s co-morbidity index :0, and investigator judged as healthy)
2. Age: 18-49 years
3. Total IgG levels in normal range (discretion of investigator according to local lab)
4. Total IgA levels (discretion of investigator according to local lab)
5. Undetectable HAI titres to the H3N2 component of the vaccines\*
6. Normal CD4+ and CD8+ T-cell and normal B-cell counts
7. Reference levels from ISO-15189 accredited T-, B- and NK-cell count routine analyses will be applied.

   * If \<20% of the first 100 screened persons apply to this criterion, this will be changed to a specific cut off based on the lowest quartile level of HAI titres to the H3N2 component of these 100 screened persons.

Exclusion Criteria:

1. Laboratory-confirmed influenza infection during the past year documented by a positive PCR test in the Danish Microbiological database or anamnestic reported influenza infection in the same period
2. Active smoker
3. BMI \> 35 kg/m2
4. Women of childbearing potential not using safe contraception, or who are pregnant, or breast-feeding
5. Any allergies to components of or contraindication for Vaxigriptetra® or Flumist® incl. previous severe adverse reactions to influenza vaccinations or components of the vaccines
6. Use of immunosuppressive drugs\* within the past 6 months or who are currently using them
7. HIV, HBV, HCV laboratory confirmed active infection at screening visit
8. Have an acute illness, including an oral temperature ≥ 38°C, within 3 days prior to vaccination
9. Have received any vaccines, including live-attenuated vaccines within 4 weeks before inclusion, or plan receipt of such vaccines within 30 days following the inclusion
10. Any known malignant neoplasm within 5 years (except basal carcinoma of the skin).
11. Severe mental illness or linguistic issues which significantly impedes cooperation
12. Inability to provide written informed consent

    * defined as: Azathioprin, methotrexate, cyclophosphamide, basiliximab, belimumab, anifrolumab, alemtuzumab, rituximab, mycophenolat, calcineurin inhibitors (ciclosporin, voclosporin and tacrolimus), mTOR inhibitors (everolimus and sirolimus), prednisolone (or any corticosteroid in doses above the equivalent of 5 mg prednisolone), TNF-α inhibitors (such as infliximab), anti-thymocyte globulin.

Primary outcomes:
measure: Day 28, mucosal immunity in nasopharynx (humoral)
timeFrame: Day -14 (baseline) [+/-5 days] vs. day +28 [+/-5 days]
Secondary outcomes:
measure: Day 7, mucosal immunity in nasopharynx (humoral)
timeFrame: Day -14 (baseline) [+/-5 days] vs. day +7 [+/-1 days]
measure: Day 28, mucosal immunity in Lower Airways (BALF) (humoral)
timeFrame: Day -14 (baseline) [+/-5 days] vs. day +28 [+/-5 days]
measure: Day 7, mucosal immunity in Lower Airways (BALF) (humoral)
timeFrame: Day -14 (baseline) [+/-5 days] vs. day +7 [+/-1 days]
measure: Rise in mucosal antibody titre (humoral)
timeFrame: Day +28 [+/- 5 days]
measure: Lower airways mucosal immunity, CD4+ (cellular)
timeFrame: Day -14 (baseline) vs. day +7
measure: Systemic immunity (blood) (cellular)
timeFrame: Day -14 (baseline) vs. day +7
Other outcomes:
measure: Early changes in local immune profiles (cellular)
timeFrame: Day -14 (baseline) vs. day +7
measure: Upper airways lymph node (Tonsil) immunity (cellular)
timeFrame: Day -14 (baseline) vs. day +7
measure: Lower airways mucosal immunity, CD8+ (cellular)
timeFrame: Day -14 (baseline) vs. day +7
measure: Further exploratory humoral characterization
timeFrame: Day -14 (baseline), day +7 day +28 [+/-5 days], day +90 and day 180 [+/-5 days]
Locations:
city: Gentofte
country: Denmark
facility: Department of Medicine, Section of Respiratory Medicine, Herlev and Gentofte Hospital
state: Copenhagen
city: Copenhagen
country: Denmark
facility: Copenhagen Hospital Biobank Unit, Department of Clinical Immunology, Rigshospitalet, Denmark
city: Copenhagen
country: Denmark
facility: Diagnostic Immunology, Department of Clinical Immunology, Rigshospitalet, Denmark
city: Copenhagen
country: Denmark
facility: Institute for Immunology and Microbiology (ISIM), Panum Institute, University of Copenhagen
city: Copenhagen
country: Denmark
facility: National Influenza Center for WHO at Statens Serum Institut (SSI)
city: Kongens Lyngby
country: Denmark
facility: Technical University of Denmark (DTU)
city: London
country: United Kingdom
facility: Imperial College
Study officials:
affiliation: Chronic Obstructive Pulmonary Disease Trial Network, Denmark
name: Jens-Ulrik Stæhr Jensen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: