GEneRating Mucosal Immunity After INfluenzA Infection and Vaccination in Lung and Lymphoid TissuE

Not Applicable

Recruiting

• Conditions: Influenza
• Interventions: Biological: FLUENZ; Biological: Influenza challenge virus

• Registration Number: NCT06620185
• Lead Sponsor: Imperial College London

Brief Summary

This experimental medicine study aims to compare immune responses in healthy adult volunteers aged 18-40 years against influenza vaccination and infection in the upper and lower respiratory tract, following administration of a live-attenuated influenza vaccine delivered by nasal spray versus influenza A (H3N2) viral challenge.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-09-25
• Study First Submitted QC: 2024-09-30
• Study First Posted: 2024-10-01
• Status Verified: 2025-04
• Study Start: 2025-04-16
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-02
• Primary Completion: 2026-01-06
• Study Completion: 2026-01-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

• Adults aged between 18-40 years inclusive
• Sero-suitable as defined by a serum micro-neutralisation titre <1:20
• Female participant who is not of child-bearing potential as assessed by an investigator OR is willing and able to use contraception as described in the protocol
• Male participants who are willing to use one of the contraception methods described in the protocol
• In good health with no clinically significant medical conditions

Exclusion Criteria

• History of clinically significant/currently active conditions;

  • Cardiovascular, thromboembolic/cerebrovascular disease.
  • Types of chronic respiratory disease in adulthood.
  • Significant wheeze in the past
  • Respiratory symptoms including wheeze, resulting in hospitalisation
  • Known bronchial hyperactivity to viruses
  • Diabetes mellitus
  • Migraine with associated symptoms like hemiplegia/vision loss. Cluster headache/migraine/prophylactic treatment for migraine.
  • History of autoimmune disease/known immunodeficiency of any cause
  • Immunosuppression.
  • Known coagulation disorder/anticoagulant therapy
  • Psychiatric illness including participants with a history of depression and/or anxiety with associated psychiatric comorbidities
  • Other major disease that, under the PI's discretion, could interfere with the participant completing the study.

• Concurrent serious illness including history of malignancy that could interfere with the study or a participant completing the study.

• Known IgA deficiency/immotile cilia syndrome/Kartagener's syndrome

• Significant abnormality altering the anatomy/function of the nose or nasopharynx, a clinically significant history of epistaxis within the last 3 months, nasal/sinus surgery within 6 months of Day 0, including nasopharyngeal malignancy, arterio-venous malformation, or undiagnosed nasopharyngeal mass

• Inhaled bronchodilator/inhaled steroid use within the last 12 months before Day 0

• Acute upper respiratory tract infection in the past 6 weeks.

• Receipt of systemic glucocorticoids (in a dose ≥ 5 mg prednisone daily or equivalent) within one month, or any other cytotoxic or immunosuppressive drug within 6 months before Day 0

• Receipt of any vaccine within 30 days of Day -14

• Any significant medical condition/prescribed drug, under the PI's discretion

• Presence of cold-like symptoms and/or fever on Day -14 or Day 0.

• Receipt of blood/blood products/loss (including blood donations) of 550 mL or more of blood during the 3 months prior to Day -14.

• Significant history/presence of drug/alcohol misuse by self-report.

• Current use of drugs through nose inhalation or inhaled route including recreational drugs.

• Regular smoking and/or vaping and/or using nicotine-containing products in the past 3 months OR >5 pack-year lifetime history by self-report (5 pack years is equivalent to one pack of 20 cigarettes per day for 5 years).

• History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food/drug, as assessed by the PI.

• Clinically active rhinitis (including hay fever)/history of moderate to severe rhinitis/history of seasonal allergic rhinitis likely to be active at the time of inclusion into the study and/or requiring regular nasal corticosteroids on an at least weekly basis, within 30 days of enrolment.

• Anyone with any of the following contraindications to receiving the Fluenz Tetra Vaccine:

  • Allergy to gentamicin, gelatin or the other ingredients of the fluenz vaccine.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LAIV	FLUENZ	-
IAV Challenge	Influenza challenge virus	-

Primary Outcome Measures

Name	Time	Method
Peak symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-40	14 days	Peak self-reported symptom scores by modified Jackson score from the viral challenge (Day 0) up to Day 14 follow-up
Average duration of symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-40	14 days	Average duration of self-reported symptom scores by modified Jackson score from the viral challenge (Day 0) up to Day 14 follow-up
To confirm symptoms related to inoculation with a GMP-adherent influenza A (H3N2) virus in healthy adults aged 18-40 by Area Under the Curve	14 days	Self-reported symptom scores by modified Jackson score from the viral challenge (Day 0) up to Day 14 follow-up (Area Under the Curve)
Peak symptoms related to inoculation with LAIV in healthy adults aged 18-40	14 days	Peak self-reported symptom scores by modified Jackson score from the vaccination (Day 0) up to Day 14 follow-up
Average duration of symptoms related to inoculation with LAIV in healthy adults aged 18-40	14 days	Average duration of self-reported symptom scores by modified Jackson score from the vaccination (Day 0) up to Day 14 follow-up (Peak, Duration, Area Under the Curve)
To confirm symptoms related to inoculation with LAIV in healthy adults aged 18-40 by Area Under the Curve	14 days	Delf-reported symptom scores by modified Jackson score from the vaccination (Day 0) up to Day 14 follow-up (Area Under the Curve)

Secondary Outcome Measures

Name	Time	Method
To assess influenza viral dynamics in upper respiratory samples	28 days	To assess influenza viral dynamics in upper respiratory samples using Viral load by RT-PCR
To assess antibody levels in blood before and after influenza challenge infection	28 days	Antibody levels by ELISA, haemagglutination inhibition assay or microneutralisation
To assess LAIV viral dynamics by RT-PCR in upper respiratory samples	28 days	To assess LAIV viral dynamics by RT-PCR in upper respiratory samples using Viral load by RT-PCR
To assess antibody levels in blood before and after LAIV	28 days	Antibody levels by ELISA, haemagglutination inhibition assay or microneutralisation

Trial Locations

Locations (1)

Imperial Clinical Research Facility, Imperial College Healthcare NHS Trust; 🇬🇧 London, United Kingdom