Vaccine Pandemic Preparedness Through Airway Immunology Characterization

NCT ID: NCT05921448

Last Updated: 2025-03-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-01
• Study Completion Date: 2026-04-30

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.

Conditions

Influenza, Human

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Vaxigripetra

This arm will receive 1 dose of 0.5 mL Vaxigripetra (intra-muscular injection) and 1 dose of 0.2 mL placebo (nasal, 1 spray in each nostril).

Group Type: EXPERIMENTAL

Vaxigripetra

Intervention Type: BIOLOGICAL

Tetravalent intramuscular vaccine. Mechanism of action: The vaccine induces an immune reaction involving antibody production.

Flumist

1 dose of 0.2 mL Flumist (nasal, 1 spray in each nostril) and 1 dose of 0.5 mL placebo (intra-muscular injection).

Group Type: EXPERIMENTAL

Flumist

Intervention Type: BIOLOGICAL

Tetravalent live attenuated influenza vaccine administered as a nasal spray. Mechanism of action: Not fully understood according to the prescribing information, but may involve influenza-specific T-cells and antibodies (serum and mucosal).

Interventions

Vaxigripetra

Tetravalent intramuscular vaccine. Mechanism of action: The vaccine induces an immune reaction involving antibody production.

Intervention Type: BIOLOGICAL

Flumist

Tetravalent live attenuated influenza vaccine administered as a nasal spray. Mechanism of action: Not fully understood according to the prescribing information, but may involve influenza-specific T-cells and antibodies (serum and mucosal).

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Chronic Obstructive Pulmonary Disease Trial Network, Denmark

OTHER

Sponsor Role: lead

The Novo Nordic Foundation

OTHER

Sponsor Role: collaborator

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jens-Ulrik Stæhr Jensen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Chronic Obstructive Pulmonary Disease Trial Network, Denmark

Locations

Copenhagen Hospital Biobank Unit, Department of Clinical Immunology, Rigshospitalet, Denmark

Copenhagen, Copenhagen, Denmark

Diagnostic Immunology, Department of Clinical Immunology, Rigshospitalet, Denmark

Copenhagen, Copenhagen, Denmark

Institute for Immunology and Microbiology (ISIM), Panum Institute, University of Copenhagen

Copenhagen, Copenhagen, Denmark

Department of Medicine, Section of Respiratory Medicine, Herlev and Gentofte Hospital

Gentofte Municipality, Copenhagen, Denmark

National Influenza Center for WHO at Statens Serum Institut (SSI)

Copenhagen, , Denmark

Technical University of Denmark (DTU)

Kongens Lyngby, , Denmark

Imperial College

London, , United Kingdom

Countries

Denmark; United Kingdom

Central Contacts

Jens-Ulrik Stæhr Jensen, MD, PhD

Role: CONTACT

jens.ulrik.jensen@regionh.dk

38673057 ext. 45

Pradeesh Sivapalan, MD, PhD

Role: CONTACT

pradeesh.sivapalan.02@regionh.dk

29880601 ext. 45

Facility Contacts

Jens-Ulrik Stæhr Jensen, MD, PhD

Role: primary

jens.ulrik.jensen@regionh.dk

38673057 ext. 45

Pradeesh Sivapalan, MD, PhD

Role: backup

pradeesh.sivapalan.02@regionh.dk

29880601 ext. 45

Other Identifiers

VAXXAIR

Identifier Type: -

Identifier Source: org_study_id