Vaccine Pandemic Preparedness Through Airway Immunology Characterization

NCT05921448 | Active Not Recruiting Early Phase 1 DMC

• 1 other identifier: VAXXAIR
• Study Type: interventional
• Target: 60
• Locations: 2 countries
• Sites: 7

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.

Conditions

Influenza, Human

Outcome Measures

Primary Outcomes (1)

• Day 28, mucosal immunity in nasopharynx (humoral)

  Time point: Comparison between day -14 (baseline) \[+/-5 days\] vs. day +28 \[+/-5 days\]. Explanation: all individuals who have a ≥-4-fold rise in (A (H3N2) haemagglutinin vaccine-specific IgA in nasopharyngeal secretions will be characterized as outcome 1. All other individuals will be characterized as outcome 0. Material: Nasopharyngeal secretions Explanation: all individuals who have a ≥-4-fold rise in (A (H3N2) haemagglutinin vaccine-specific IgA in nasal secretions will be characterized as outcome 1. All other individuals will be characterized as outcome 0. Material: nasopharyngeal secretion.

  Day -14 (baseline) [+/-5 days] vs. day +28 [+/-5 days]

Secondary Outcomes (6)

• Day 7, mucosal immunity in nasopharynx (humoral)

  Day -14 (baseline) [+/-5 days] vs. day +7 [+/-1 days]

• Day 28, mucosal immunity in Lower Airways (BALF) (humoral)

  Day -14 (baseline) [+/-5 days] vs. day +28 [+/-5 days]

• Day 7, mucosal immunity in Lower Airways (BALF) (humoral)

  Day -14 (baseline) [+/-5 days] vs. day +7 [+/-1 days]

• Rise in mucosal antibody titre (humoral)

  Day +28 [+/- 5 days]

• Lower airways mucosal immunity, CD4+ (cellular)

  Day -14 (baseline) vs. day +7

Other Outcomes (4)

• Early changes in local immune profiles (cellular)

  Day -14 (baseline) vs. day +7

• Upper airways lymph node (Tonsil) immunity (cellular)

  Day -14 (baseline) vs. day +7

• Lower airways mucosal immunity, CD8+ (cellular)

  Day -14 (baseline) vs. day +7

Study Arms (2)

Vaxigripetra

EXPERIMENTAL

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).

Biological: Vaxigripetra

Flumist

EXPERIMENTAL

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

Biological: Flumist

Interventions

Vaxigripetra BIOLOGICAL

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

Vaxigripetra

Flumist 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).

Flumist

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy individuals (Charlson´s co-morbidity index :0, and investigator judged as healthy)
• Age: 18-49 years
• Total IgG levels in normal range (discretion of investigator according to local lab)
• Total IgA levels (discretion of investigator according to local lab)
• Undetectable HAI titres to the H3N2 component of the vaccines\*
• Normal CD4+ and CD8+ T-cell and normal B-cell counts
• 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.

You may not qualify if:

• 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
• Active smoker
• BMI \> 35 kg/m2
• Women of childbearing potential not using safe contraception, or who are pregnant, or breast-feeding
• Any allergies to components of or contraindication for Vaxigriptetra® or Flumist® incl. previous severe adverse reactions to influenza vaccinations or components of the vaccines
• Use of immunosuppressive drugs\* within the past 6 months or who are currently using them
• HIV, HBV, HCV laboratory confirmed active infection at screening visit
• Have an acute illness, including an oral temperature ≥ 38°C, within 3 days prior to vaccination
• Any known malignant neoplasm within 5 years (except basal carcinoma of the skin).
• Severe mental illness or linguistic issues which significantly impedes cooperation
• 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.

Sponsors & Collaborators

• The Novo Nordic Foundation: collaborator
• Copenhagen Respiratory Research: lead

Study Sites (7)

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

Copenhagen, Copenhagen, 2100, Denmark

Location

Diagnostic Immunology, Department of Clinical Immunology, Rigshospitalet, Denmark

Copenhagen, Copenhagen, 2100, Denmark

Location

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

Copenhagen, Copenhagen, 2100, Denmark

Location

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

Gentofte Municipality, Copenhagen, 2900, Denmark

Location

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

Copenhagen, 2300, Denmark

Location

Technical University of Denmark (DTU)

Kongens Lyngby, 2800, Denmark

Location

Imperial College

London, W12 0NN, United Kingdom

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

FluMist

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Jens-Ulrik Stæhr Jensen, MD, PhD

  Chronic Obstructive Pulmonary Disease Trial Network, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) . Encryption will be through a website (REDCap).
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: June 18, 2023
• First Posted: June 27, 2023
• Study Start: May 19, 2025
• Primary Completion (Estimated): July 27, 2026
• Study Completion (Estimated): July 27, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); DK (6)