Novel Mucosal Correlates Of RSV Protection In Older Adults

Respiratory syncytial virus (RSV) is one of the most common causes of chest infection worldwide. Despite this, it remains an underappreciated health problem, with the first effective RSV vaccines only approved by the FDA in May 2023 and unlikely to be widely available for some time. Although RSV infection is most frequent in young children, most deaths occur in older adults, particularly in those with underlying heart and lung disease. This is believed to be due in part to the ageing immune system's reduced ability to protect against infection and symptomatic disease.

However, little is known about the way human immune responses to RSV infection in older individuals differ from those of younger people. Further understanding of the mechanisms underlying immunity and potential impairments in these higher-risk people are therefore necessary. This project aims to study the factors that influence whether or not older people develop symptomatic RSV disease in healthy older volunteers after being given an RSV-induced common cold. Samples will be taken from the blood and nose in order to identify changes in the immune system associated with susceptibility or protection in older adults. Participants will be carefully screened to ensure there are no underlying health problems that might make them more at risk of severe disease and will be monitored closely throughout the course of infection. It is anticipated that differences in immune markers in the nose and/or blood of healthy older people will predict whether or not such individuals become infected or develop symptoms. By analysing the networks of genes that are switched on and off, the aim is to identify the pathways in the immune system responsible for these differences, to ultimately develop improved diagnostic tests, vaccines and treatments.


Eligibility Criteria:
Inclusion Criteria:

* Healthy persons aged 65 to 75 years, able to give informed consent
* Non-smokers or ex-smokers with a pack year history of 10 or less
* Spirometry within the normal range for age and height (+/- 15%)
* Forced Expiratory Volume / Forced Vital Capacity (FEV1/FVC) \>70% without bronchodilator
* Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the minimum of 4 weeks prior to screening

Exclusion Criteria:

* Chronic respiratory disease (asthma, chronic obstructive pulmonary disease, rhinitis, sinusitis) in adulthood
* Inhaled bronchodilator or steroid use within the last 12 months
* Habitual use of any medication or other product (prescription or over the counter) for symptoms of rhinitis or nasal congestion within the last 3 months
* Acute upper respiratory infection (URI or sinusitis) in the past 6 weeks
* Participants with allergic symptoms present at baseline
* Clinically relevant abnormality on chest X-ray
* Those in close domestic contact (i.e. sharing a household with, caring for, or daily face to face contact) with children under 3 years, clinically vulnerable and/or immunosuppressed persons, or those with chronic respiratory disease
* Participants with known or suspected immune deficiency
* 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 challenge
* Known Immunoglobulin A (IgA) deficiency, immotile cilia syndrome, or Kartagener's syndrome
* History of frequent nose bleeds
* Any significant medical condition or prescribed drug deemed by a study doctor to make the participant unsuitable for the study
* Recent or current use of recreational drugs, confirmed by a positive urine drug screen
* History of difficult blood draw, syncope or poor tolerance of sampling procedures