Inclusion Criteria:
1. Aged between 65 to 75years (inclusive) at Day 0.
2. Willing and able to commit to participation in the study.
3. Adequate understanding of the study, the procedures involved, and able to provide written informed consent prior to any study procedures.
4. In good health with no history of clinically significant medical conditions (as described in exclusion criteria) that would interfere with participant safety. A forced expiratory volume in 1 second (FEV1) and a forced vital capacity (FVC) \<80% of predicted value calculated using ATS/ERS guidance.
Exclusion Criteria:
1. Any significant medical condition or prescribed drug deemed by the Investigator to deem the participant unsuitable for the study.
2. History or evidence of any clinically significant or currently active:
1. Cardiovascular, thromboembolic or cerebrovascular disease.
2. Chronic respiratory disease (e.g. asthma, COPD, rhinitis, sinusitis, reactive airway disease, pulmonary hypertension or a chronic lung condition) in adulthood (a history of childhood asthma without respiratory disease in adulthood may be accepted at the PIs discretion).
3. Significant or severe wheeze, or respiratory symptoms (including wheeze) which has ever resulted in hospitalisation.
4. Known bronchial hyperactivity to viruses.
5. Diabetes mellitus.
6. Migraine with associated neurological symptoms such as hemiplegia or vision loss. Cluster headache/migraine or prophylactic treatment for migraine.
7. History or evidence of autoimmune disease or known/suspected immunodeficiency of any cause, including asplenia or history of recurrent severe infections.
8. Immunosuppression of any type.
9. Known IgA deficiency, immotile cilia syndrome, or Kartagener's syndrome.
10. Known coagulation disorder or anticoagulant therapy.
11. Psychiatric illness including participants with a history of depression and/or anxiety with associated severe psychiatric comorbidities, for example psychosis. Consider exclusion in the following cases: Participants with history of anxiety-related symptoms of any severity within the last 2 years if the Generalized Anxiety Disorder-7 score is ≥4; Participants with a history of depression of any severity within the last 2 years if the Patient Health Questionnaire-9 score is ≥4; . Severe claustrophobia
12. Other major disease that, in the opinion of the Investigator, could interfere with a participant completing the study and necessary investigations.
13. Concurrent serious illness including history of malignancy that could interfere with the aims of the study or a participant completing the study.
Permissible stable conditions that are well controlled might not be exclusionary and will be assessed by the PI on a case-by-case basis. These include, but will not be limited to: well controlled Hypertension, Sensitive Bladder, Hiatus Hernia, Vitamin D Deficiency, Diverticulitis, Renal Calculi, Depression (well managed), Perioral Dermatitis, Hypercholesterolemia (diet or well medically controlled), Macular Degeneration, Mild Arthritis.
3. Any significant abnormality altering the anatomy or function of the nose or nasopharynx in a substantial way, including nasopharyngeal malignancy, arterio-venous malformation, or undiagnosed nasopharyngeal mass.
4. A history of clinically significant epistaxis (large nosebleeds) within 3 months of Day 0.
5. Nasal or sinus surgery within 3 months of Day 0.
6. Any anatomic or neurologic abnormality impairing the gag reflex or associated with increased risk of aspiration.
7. 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 prior to Day 0.
8. A history of inhaled bronchodilator or inhaled steroid use within the prior 12 months to Day -14.
9. Receipt of any vaccine within 30 days of Day -14 or planned during the study period, until the last follow-up visit (Day 90).
10. Participation in an investigational drug or device study within 3 months prior to Day 0.
11. Receipt of blood or blood products, or loss (including blood donations) of 550 mL or more of blood during the 6 months prior to Day -14.
12. History of difficult blood draw, syncope or poor tolerance of sampling procedures as assessed by clinical study team.
13. History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI.
14. Allergic symptoms present at baseline (at screening, day -14 or day 0).
15. Clinically active rhinitis (including hay fever) or history of moderate to severe rhinitis, or 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.
16. Habitual use of any medication or other product (prescription or over the counter) for symptoms of rhinitis or nasal congestion the 3 months prior to Day -14.
17. Receipt of RSV vaccine at any time or planned RSV vaccination in the 3 months following inoculation.
18. Virologically confirmed RSV infection within 6 months of Day 0.
19. Prior inoculation with a virus from the same virus family (Pneumoviridiae) as the challenge virus.
20. Prior participation in another controlled human infection study with a respiratory virus in the preceding 6 months taken from the date of viral challenge in the previous study to the date of expected viral challenge in this study.
21. Acute upper respiratory infection (URI or sinusitis) in the 6 weeks prior to Day-14 baseline visit.
22. Presence of cold-like symptoms and/or fever (defined as participant presenting with a temperature reading of \>37.9ºC) on Day -14, Day -1 or Day 0.
23. A respiratory PCR test that is indicative of Influenza, RSV or other respiratory virus infection, including asymptomatic infections, determined by a test on admission to quarantine (Day -1).
24. Clinically relevant abnormality on chest X-ray.
25. A total body weight of ≤ 50kg and a Body Mass Index (BMI) ≤18 kg/m2 or ≥28 kg/m2.
• The upper limit of BMI may be increased to ≤ 30kg/m2 at the PI's discretion, in the case of physically fit muscular individual or other variation of normal).
26. Any abnormal finding on screening safety blood tests deemed to be clinically significant by the Investigator including positive HIV, active/chronic hepatitis B or C test.
27. Any ECG abnormality deemed to be clinically significant by the Investigator.
28. Significant history or presence of drug or alcohol misuse.
1. Participants will be required to have a negative urine drug test at screening. If positive, this will be exclusionary.
2. Current use of more than 21 units alcohol per week, drug abuse, or regular use of sedatives, hypnotics, tranquilisers or any other addictive agent are exclusionary.
29. Current use of any recreational drugs, including injected, taken through the nose or inhaled route.
30. Regular smoking and/or vaping and/or using other nicotine-containing products in the past 3 months OR:
1. \>5 pack-year lifetime history by self-report (5 pack years is equivalent to one pack of 20 cigarettes per day for 5 years).
2. Participants will be required to have a negative urine cotinine test at screening. If positive, this will be exclusionary.
31. Those in close domestic contact (i.e. sharing a household with, caring for, or daily face to face contact) with children under 4 years, clinically vulnerable and/or immunosuppressed persons, or those with chronic respiratory disease for 30 days after RSV B inoculation.
