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

This experimental medicine study aims to compare immune responses in healthy adult volunteers aged 18-55 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.

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.