Characterization of antibodies in the nose after influenza vaccination

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leids Universitair Medisch Centrum (LUMC)

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

19 Sep 2025 → ongoing

Decision date (initial)

2025-05-26

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

ZonMW VENI

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis

The proposed study aims to investigate the quantitative and qualitative differences in antibody responses between intranasal and intramuscular vaccination with the influenza vaccine.

Conditions and MedDRA coding

healthy individuals

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Participants between 18 and 40 years old
2. Male and female sex
3. Participants that are generally healthy without substantial comorbidities, especially no primary or secondary immunodeficiencies

Exclusion criteria 16

1. Previous influenza vaccination < 4 months before the study
2. Previous influenza infection < 4 months before the study
3. Vaccinations with other vaccines <2 months before inclusion
4. Incompetence to provide informed consent prior or during study
5. History of severe nose bleedings
6. Symptoms of a respiratory tract infection or common cold in the past 2 weeks
7. Documented primary or secondary immunodeficiencies and individuals using methotrexate
8. Daily smoking (including vapes) for at least one consecutive month in the last 2 year
9. Pregnancy during the time of the study
10. Breastfeeding during the course of the study
11. Known chicken-egg allergy
12. Known hypersensitivity to any other of the vaccine components
13. Use of anticoagulants
14. Use of oral corticosteroids or antibiotics in the past 6 weeks
15. Diagnosed with chronic rhinosinusitis, allergic rhinitis and or allergic asthma
16. A condition that requires salicylate treatment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The main endpoint is the fold change in influenza specific IgA levels in nasal fluid of healthy individuals at day 21 after receiving an intranasal influenza vaccination compared to an intramuscular influenza vaccination.

Secondary endpoints 12

1. Determination of influenza-specific IgA and IgG glycosylation in nasal fluid and blood and correlated this with the total IgA and IgG glycosylation in both groups [timeframe: Baseline, 1-10, 14, 21, and 70 days after vaccination].
2. Correlate antibody (IgA and IgG) concentrations in nasal fluid and blood after vaccination in both groups [timeframe: Baseline, 1-10, 14, 21, and 70 days after vaccination].
3. Profiling of glycosylation of total and antigen-specific IgG and IgA in saliva in each group and correlated this to results in blood and nasal fluid [timeframe: Baseline, 1-10, 14, 21, and 70 days after vaccination].
4. Transcriptomic profiling (single-cell RNA-sequencing (scRNA-seq) and B-cell receptor sequencing (BCRseq) of B cells in the nasopharyngeal samples and blood in both groups. [Timeframe: baseline, 7,14,21, and 70 days after vaccination].
5. In dept (gene expression) profiling of (innate) immune cells, e.g. glycosyltransferase expression and spectral flow panels in the nasopharyngeal adenoid samples and blood in each group and correlate this between the two compartments [timeframe: Baseline, 7, 14, 21, and 70 days after vaccination].
6. In dept molecular detection of microbiota and the presence of viral infections in each group [timeframe: Baseline, 7, 14, 21, and 70 days after vaccination].
7. Analysis of secreted immune mediators (e.g. cytokines, antimicrobial defence molecules, antibodies and metabolites) in nasal lining fluid, saliva, and blood of each group and the correlate with (innate) immune cells and antibody glycosylation [timeframe: Baseline, 1-10, 14, 21, and 70 days after vaccination].
8. Association of antibody glycosylation with covariates, such as biological age and sex, (innate) immune populations, and other immune parameters [timeframe: Baseline, 1-10, 14, 21, and 70 days after vaccination].
9. Correlation of host immune response after intranasal vaccination (this study) with the host immune response in a cohort of children that received a LIAV (LION study).
10. Nasal shedding of all four strains of influenza post-LAIV, measured using daily collected nasosorptions and analyzed with RT-PCR techniques [timeframe: Baseline, 1-10 days after vaccination].
11. Explorative endpoint: Transcriptomic cluster composition, as frequency of T cells subsets, and clonality of nasal (inferior turbinate) and blood T cell populations in both groups [timeframe: Baseline, 7, 14, 21, and 70 days after vaccination].
12. Explorative endpoint: In dept (gene expression) profiling of (innate) immune cells, e.g. Activator Induced Marker (AIM)-assays and spectral flow panels in the inferior turbinate and blood in each group and correlate this between compartments [timeframe: Baseline, 7, 14, 21, and 70 days after vaccination].

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leids Universitair Medisch Centrum (LUMC)

Sponsor organisation

Leids Universitair Medisch Centrum (LUMC)

Address

Albinusdreef 2

City

Leiden

Postcode

2333 ZA

Country

Netherlands

Scientific contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

J.W. Hoepel

Public contact point

Organisation

Leids Universitair Medisch Centrum (LUMC)

Contact name

J.W. Hoepel

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications