This is a human challenge sequential cohort study involving healthy, non-smoking older adults aged 65-75 years. We aim to enrol 20 participants. There will be a sentinel cohort of 6 participants at the beginning of the study (Group 1). If no pausing rules are met, the remaining 14 participants will be enrolled for a total of 20 enrolled participants (Group 2).
The study will consist of three main phases: (1) screening and baseline, (2) inoculation and quarantine, and (3) follow up.
All participants will attend a screening visit for a comprehensive health assessment to confirm eligibility.
If eligible, participants will take part in an inpatient stay in a quarantine unit, where they will be inoculated with 105 plaque-forming units of RSV B-I54 by intranasal drops. The inoculation dose has been determined in the earlier mentioned outpatient study of the same virus strain, in healthy young adults.
Due to the older age range and potentially increased risk of more severe disease, participants will remain within the quarantine unit for 10-days post inoculation and will be closely monitored by clinical review and self-completed symptom diaries. Participants will undergo daily sample collection and will remain in quarantine until the discharge criteria are met at Day 10.
After discharge, participants will attend follow-up visits at Day 14, Day 28, and Day 90.
Participants in Group 2 will have an additional baseline visit at Day -14 where blood, respiratory (nose and throat) and lower airway (bronchoscopy) samples will be collected. Group 2 participants will also undergo a second bronchoscopy during the inpatient period and the third and final bronchoscopy at Day 28.
Clinical outcomes will be determined by symptomatology and viral detection in nasal lavage using quantitative PCR. Based on the first-in-human RSV B characterisation study and recent elderly RSV A challenge data, we anticipate approximately 74% attack rate, with a range of mild-moderate symptoms in the infected individuals. Symptoms typically commence 3 days post-inoculation and worsen to peak around days 5-9 before rapidly resolving without treatment. Timing of viral shedding is expected to correlate closely with symptoms.
Inclusion Criteria:
Exclusion Criteria:
Any significant medical condition or prescribed drug deemed by the Investigator to deem the participant unsuitable for the study.
History or evidence of any clinically significant or currently active:
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.
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.
A history of clinically significant epistaxis (large nosebleeds) within 3 months of Day 0.
Nasal or sinus surgery within 3 months of Day 0.
Any anatomic or neurologic abnormality impairing the gag reflex or associated with increased risk of aspiration.
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.
A history of inhaled bronchodilator or inhaled steroid use within the prior 12 months to Day -14.
Receipt of any vaccine within 30 days of Day -14 or planned during the study period, until the last follow-up visit (Day 90).
Participation in an investigational drug or device study within 3 months prior to Day 0.
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.
History of difficult blood draw, syncope or poor tolerance of sampling procedures as assessed by clinical study team.
History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI.
Allergic symptoms present at baseline (at screening, day -14 or day 0).
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.
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.
Receipt of RSV vaccine at any time or planned RSV vaccination in the 3 months following inoculation.
Virologically confirmed RSV infection within 6 months of Day 0.
Prior inoculation with a virus from the same virus family (Pneumoviridiae) as the challenge virus.
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.
Acute upper respiratory infection (URI or sinusitis) in the 6 weeks prior to Day-14 baseline visit.
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.
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).
Clinically relevant abnormality on chest X-ray.
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).
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.
Any ECG abnormality deemed to be clinically significant by the Investigator.
Significant history or presence of drug or alcohol misuse.
Current use of any recreational drugs, including injected, taken through the nose or inhaled route.
Regular smoking and/or vaping and/or using other nicotine-containing products in the past 3 months OR:
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.
polly.fox@imperial.ac.uk02033131282
A sentinel group of n=6 will be enrolled and will not undergo bronchoscopies
14 participants will be enrolled and be given the same intervention and undergo the same sampling and assessement but with additional bronchoscopy sampling at 3 timepoints
Respiratory Syncytial Virus Human Challenge in Healthy Adult Volunteers
Challenge Infection of Healthy Adult Volunteers With RSV A2
Novel Mucosal Correlates Of RSV Protection In Older Adults
The Impact of Age on Adaptive Immunity in Adults Infected With Respiratory Syncytial Virus
RSV Challenge in Healthy Adults
Study of RSVpreF Vaccination and RSV Challenge in Healthy Adults
RSV Study in Adults 60 to 75 Years of Age
Inpatient Challenge Study of rRSV A/Maryland/001/11, a Human Respiratory Syncytial Virus Challenge Strain, Administered to Healthy Adult Volunteers