Comparing immune responses to influenza vaccination and infection in healthy adults

A Two-arm, Non-randomised, Open-label Experimental Medicine Study to Compare Immune Responses Between Healthy Volunteers Aged 18-55years Receiving Either an Intranasal Live-attenuated Influenza Vaccine or Viral Challenge With GMP Influenza A/Belgium/4217/2015 (H3N2)

This study tests how healthy adults respond to the flu vaccine and a flu virus to see which one helps their immune system better.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: Imperial College London (Academic / other)
• Drugs / interventions: prednisone
• Locations: 1 site (London)
• Trial ID: NCT06620185 on ClinicalTrials.gov

What this trial studies

This experimental study investigates the immune responses of healthy adult volunteers aged 18-40 years to influenza vaccination and infection. Participants will receive a live-attenuated influenza vaccine via nasal spray and will also be exposed to an influenza A (H3N2) viral challenge. The study aims to assess how these two methods of exposure affect immune responses in both the upper and lower respiratory tracts. The findings could provide insights into the effectiveness of vaccination versus natural infection in generating mucosal immunity.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy adults aged 18-40 years who meet specific serological and health criteria.

Not a fit: Patients with significant medical conditions or a history of chronic respiratory diseases may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance our understanding of how to improve influenza vaccination strategies and mucosal immunity.

How similar studies have performed: Other studies have explored similar approaches to understanding immune responses to influenza, indicating potential for success in this area.

Eligibility criteria

Inclusion Criteria:

* Adults aged between 18-55 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.

Where this trial is running

London

• Imperial Clinical Research Facility, Imperial College Healthcare NHS Trust — London, United Kingdom (Recruiting)

Study contacts

• Principal investigator: Christopher Chiu — Imperial College London
• Study coordinator: Polly Fox, MSc

Conditions Influenza; LAIV; Challenge; Vaccine; Flu