Vaccine Pandemic Preparedness Through Airway Immunology Characterization
- Conditions
- Influenza, Human
- Interventions
- Biological: Vaxigripetra
- Registration Number
- NCT05921448
- Lead Sponsor
- Chronic Obstructive Pulmonary Disease Trial Network, Denmark
- 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 60
-
Healthy individuals (Charlson´s co-morbidity index :0, and investigator judged as healthy)
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Age: 18-49 years
-
Total IgG levels in normal range (discretion of investigator according to local lab)
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Total IgA levels (discretion of investigator according to local lab)
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Undetectable HAI titres to the H3N2 component of the vaccines*
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Normal CD4+ and CD8+ T-cell and normal B-cell counts
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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.
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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
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Active smoker
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BMI > 35 kg/m2
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Women of childbearing potential not using safe contraception, or who are pregnant, or breast-feeding
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Any allergies to components of or contraindication for Vaxigriptetra® or Flumist® incl. previous severe adverse reactions to influenza vaccinations or components of the vaccines
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Use of immunosuppressive drugs* within the past 6 months or who are currently using them
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HIV, HBV, HCV laboratory confirmed active infection at screening visit
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Have an acute illness, including an oral temperature ≥ 38°C, within 3 days prior to vaccination
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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
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Any known malignant neoplasm within 5 years (except basal carcinoma of the skin).
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Severe mental illness or linguistic issues which significantly impedes cooperation
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Flumist 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). Vaxigripetra 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).
- Primary Outcome Measures
Name Time Method Day 28, mucosal immunity in nasopharynx (humoral) 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.
- Secondary Outcome Measures
Name Time Method Day 7, mucosal immunity in Lower Airways (BALF) (humoral) 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.Rise in mucosal antibody titre (humoral) 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 secretionDay 7, mucosal immunity in nasopharynx (humoral) 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.Systemic immunity (blood) (cellular) 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/3073/2013Day 28, mucosal immunity in Lower Airways (BALF) (humoral) 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.Lower airways mucosal immunity, CD4+ (cellular) 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
Trial Locations
- Locations (7)
National Influenza Center for WHO at Statens Serum Institut (SSI)
🇩🇰Copenhagen, Denmark
Department of Medicine, Section of Respiratory Medicine, Herlev and Gentofte Hospital
🇩🇰Gentofte, Copenhagen, Denmark
Copenhagen Hospital Biobank Unit, Department of Clinical Immunology, Rigshospitalet, Denmark
🇩🇰Copenhagen, Denmark
Diagnostic Immunology, Department of Clinical Immunology, Rigshospitalet, Denmark
🇩🇰Copenhagen, Denmark
Institute for Immunology and Microbiology (ISIM), Panum Institute, University of Copenhagen
🇩🇰Copenhagen, Denmark
Technical University of Denmark (DTU)
🇩🇰Kongens Lyngby, Denmark
Imperial College
🇬🇧London, United Kingdom