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Préparation à une pandémie vaccinale grâce à la caractérisation immunologique des voies respiratoires (VAXXAIR)

4 novembre 2026 mis à jour par: Copenhagen Respiratory Research

Analyse immunologique approfondie de l'immunité des voies respiratoires après un vaccin antigrippal nasal vivant atténué et intramusculaire

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.

Aperçu de l'étude

Statut

Actif, ne recrute pas

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

60

Phase

  • Première phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • Danemark
      • Copenhagen, Danemark, 2300
        • National Influenza Center for WHO at Statens Serum Institut (SSI)
      • Kongens Lyngby, Danemark, 2800
        • Technical University of Denmark (DTU)
    • Copenhagen
      • Copenhagen, Copenhagen, Danemark, 2100
        • Copenhagen Hospital Biobank Unit, Department of Clinical Immunology, Rigshospitalet, Denmark
      • Copenhagen, Copenhagen, Danemark, 2100
        • Diagnostic Immunology, Department of Clinical Immunology, Rigshospitalet, Denmark
      • Copenhagen, Copenhagen, Danemark, 2100
        • Institute for Immunology and Microbiology (ISIM), Panum Institute, University of Copenhagen
      • Gentofte Municipality, Copenhagen, Danemark, 2900
        • Department of Medicine, Section of Respiratory Medicine, Herlev and Gentofte Hospital
  • Royaume-Uni
      • London, Royaume-Uni, W12 0NN
        • Imperial College

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 49 ans (Adulte)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: La prévention
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: 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).
Biologique: Vaxigripetra

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

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Day 28, mucosal immunity in nasopharynx (humoral)
Délai: Day -14 (baseline) [+/-5 days] vs. day +28 [+/-5 days]

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]

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Day 7, mucosal immunity in nasopharynx (humoral)
Délai: Day -14 (baseline) [+/-5 days] vs. day +7 [+/-1 days]

Time point: Comparison between day -14 (baseline) [+/-5 days] vs. day +7 [+/-1 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 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 +7 [+/-1 days]
Day 28, mucosal immunity in Lower Airways (BALF) (humoral)
Délai: Day -14 (baseline) [+/-5 days] vs. day +28 [+/-5 days]

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 will be characterized as outcome 0.
Day -14 (baseline) [+/-5 days] vs. day +28 [+/-5 days]
Day 7, mucosal immunity in Lower Airways (BALF) (humoral)
Délai: Day -14 (baseline) [+/-5 days] vs. day +7 [+/-1 days]

Time point: Comparison between day -14 (baseline) [+/-5 days] vs. day +7 [+/-1 days].

Explanation: all individuals who have a ≥-4-fold rise in (A (H3N2) haemagglutinin vaccine-specific IgA in BALF will be characterized as outcome 1. All other individuals will be characterized as outcome 0.
Day -14 (baseline) [+/-5 days] vs. day +7 [+/-1 days]
Rise in mucosal antibody titre (humoral)
Délai: Day +28 [+/- 5 days]

Hypothesis: Intranasally administered LAIV influenza vaccine will more often produce a ≥-4-fold rise in mucosal antibody titre against each of the remaining (non-H3N2) vaccine virus haemagglutinin antigens vaccine-specific antibody (IgG (when BALF) and IgA (when nasopharyngeal)) titres in respiratory secretions compared to intramuscular IIV tetravalent influenza vaccine.

Time points: Day -14 (baseline), and i) day 28 [+/-5 days] ii) and day 7 [+/-1 day] after vaccination.

Antigens: 1) A (H1N1) ; 2) B/Austria/1359417/2021 ; 3) B/Phuket/3073/2013 Material: BALF and nasopharyngeal secretion
Day +28 [+/- 5 days]
Lower airways mucosal immunity, CD4+ (cellular)
Délai: Day -14 (baseline) vs. day +7

Hypothesis: Intranasally administered LAIV influenza vaccine will lead to a higher number of Antigen activated* CD4+ T-lymphocytes in BALF measured at day -14 (baseline) vs. day +7 as compared to intramuscular IIV tetravalent influenza vaccine.

Explanation: Fractions of CD4+ T-lymphocytes, that are antigen activated against an antigen pool composed of the antigens in the two utilized vaccines, will be measured at day -14 (baseline) and day +7.

Fold changes will be compared between vaccine arms. Material: BALF.

* A (H1N1) - A (H3N2) • B/Austria/1359417/2021 • B/Phuket/3073/2013
Day -14 (baseline) vs. day +7
Systemic immunity (blood) (cellular)
Délai: Day -14 (baseline) vs. day +7

Hypothesis: Intranasally administered LAIV influenza vaccine will lead to a higher number of Antigen activated* CD4+ T-lymphocytes in blood measured at day -14 (baseline) vs. day +7 as compared to intramuscular IIV tetravalent influenza vaccine.

Explanation: Fractions of CD4+ T-lymphocytes, that are antigen activated against an antigen pool composed of the antigens in the two utilized vaccines, will be measured at day -14 (baseline) and day +7.

Fold changes will be compared between vaccine arms. Material: Blood

* A (H1N1) - A (H3N2) • B/Austria/1359417/2021 • B/Phuket/3073/2013
Day -14 (baseline) vs. day +7

Autres mesures de résultats

Mesure des résultats
Description de la mesure
Délai
Early changes in local immune profiles (cellular)
Délai: Day -14 (baseline) vs. day +7

Hypothesis and explanation: Airway-delivered LAIV vaccine (Flumist) will induce early antigen specific T- lymphocytes as well as resident memory T- and B-cells locally in the respiratory tract that is characterized by activated TRM and TFH in BALF and mediastinal lymph nodes, and with higher levels of CXCR3pos-B-cells and BRM in BALF and respiratory mucosal tissue and mediatinal lymph nodes compared to that of intramuscular delivered trivalent flu vaccine.

Material: BALF
Day -14 (baseline) vs. day +7
Upper airways lymph node (Tonsil) immunity (cellular)
Délai: Day -14 (baseline) vs. day +7

Hypothesis: Intranasally administered LAIV influenza vaccine will lead to a higher number of Antigen activated* CD4+ T-lymphocytes in lymphoid tissue from tonsils measured at day -14 (baseline) vs. day +7 as compared to intramuscular IIV tetravalent influenza vaccine.

Explanation: Fractions of CD4+ and CD8+ T-lymphocytes, that are antigen activated against an antigen pool composed of the antigens in the two utilized vaccines, will be compared between day -14 (baseline) and day +7.

Material: Lymphoid tissue from tonsils. Analysis of this hypothesis depends on feasibility (enough material)

* A (H1N1) - A (H3N2) • B/Austria/1359417/2021 • B/Phuket/3073/2013
Day -14 (baseline) vs. day +7
Lower airways mucosal immunity, CD8+ (cellular)
Délai: Day -14 (baseline) vs. day +7

Hypothesis: Intranasally administered LAIV influenza vaccine will lead to a higher number of Antigen activated* CD8+ T-lymphocytes in BALF measured at day -14 (baseline) vs. day +7 as compared to intramuscular IIV tetravalent influenza vaccine.

Explanation: Fractions of CD8+ T-lymphocytes, that are antigen activated against an antigen pool composed of the antigens in the two utilized vaccines, will be measured at day -14 (baseline) and day +7.

Fold changes will be compared between vaccine arms. Material: BALF.

* A (H1N1) - A (H3N2) • B/Austria/1359417/2021 • B/Phuket/3073/2013
Day -14 (baseline) vs. day +7
Further exploratory humoral characterization
Délai: Day -14 (baseline), day +7 day +28 [+/-5 days], day +90 and day 180 [+/-5 days]

Haemagglutinin antigens vaccine-specific antibody (IgG) titres in serum (HAI). This will be analysed in the following analyses:

A. Number of participants with ≥-4-fold rise in serum antibody titres against each vaccine virus* B. Categorical and scalar associations between vaccine virus shedding (measured at days +1, +3, and +7 post-vaccination) and cellular and humoral immune responses.

C. Proportion of study enrolled subjects achieving a HAI titre of ≥1:40 measured using antibody titre measured at -14 (baseline), day +7 day +28 [+/-5 days], day +90 and day 180 [+/-5 days] after vaccination.

* A (H1N1) - A (H3N2) • B/Austria/1359417/2021 • B/Phuket/3073/2013
Day -14 (baseline), day +7 day +28 [+/-5 days], day +90 and day 180 [+/-5 days]

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Copenhagen Respiratory Research

Collaborateurs

The Novo Nordic Foundation

Les enquêteurs

  • Chercheur principal: Jens-Ulrik Stæhr Jensen, MD, PhD, Chronic Obstructive Pulmonary Disease Trial Network, Denmark

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

19 mai 2025

Achèvement primaire (Estimé)

31 octobre 2032

Achèvement de l'étude (Estimé)

31 octobre 2032

Dates d'inscription aux études

Première soumission

18 juin 2023

Première soumission répondant aux critères de contrôle qualité

18 juin 2023

Première publication (Réel)

27 juin 2023

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

6 novembre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

4 novembre 2026

Dernière vérification

1 mars 2026

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • VAXXAIR

Plan pour les données individuelles des participants (IPD)

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Description du régime IPD

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Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

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Étudie un produit d'appareil réglementé par la FDA américaine

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