The Impact of Age on Adaptive Immunity in Adults Infected With Respiratory Syncytial Virus (INFLAMMAGE)

Imperial College London

Status

Completed

Conditions

RSV Infection

Treatments

Biological: RSV A Memphis 37

Study type

Interventional

Funder types

Other

Identifiers

NCT03728413

14SM2070

Details and patient eligibility

About

This study will for the first time systematically investigate the immune responses in an elderly cohort challenged with a well-defined RSV inoculum. With a global aging population and continuing difficulties in generating vaccines that can reliably induce protective immunity in the elderly, these data will indicate the targets at which development of vaccines against RSV and other infections should be directed.

Full description

Respiratory syncytial virus (RSV) is one of the most common causes of chest infection worldwide, with 64 million episodes and 160,000 deaths each year. Despite this, it remains an underappreciated health problem and there are currently no specific treatments or vaccines against it. Although RSV infection is most frequent in young children, the majority of 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 role of T cells (which destroy virus-infected cells and are likely to be essential for recovery from infection) in healthy older volunteers after they have been given an RSV-induced common cold. Samples will be taken from the blood and respiratory tract in order to identify the differences in T cell responses that occur in older adults compared with their younger counterparts. Participants will be carefully screened to ensure they do not have any underlying health problems that might make them more at risk of severe disease and will be monitored closely throughout the course of infection. The investigators anticipate that T cell function even in healthy older individuals will be impaired compared to young adults, thus contributing in those with additional health problems to more severe disease. By analysing the networks of genes that are switched on and off, the investigators aim to identify the particular defects underlying these functional defects in order to ultimately define targets for novel treatments and T cell-stimulating vaccines.

Enrollment

28 patients

Sex

All

Ages

60 to 75 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Healthy persons aged 60 to 75 years, able to give informed consent
Non smokers or ex-smokers with smokers with less than or equal to 5 pack years smoking history.
Spirometry within the normal range for age and height (+/- 15%)
FEV1/FVC >70% pre-bronchodilator

Exclusion criteria

Chronic respiratory disease (asthma, COPD, 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
Subjects 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, other elderly adults (>65 years), immunosuppressed persons, or those with chronic respiratory disease
Subjects 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 IgA deficiency, immotile cilia syndrome, or Kartagener's syndrome
History of frequent nose bleeds
Any significant medical condition or prescribed drug deemed by the study doctor to make the participant unsuitable for the study
Women of childbearing potential must have a negative hCG urine pregnancy test *
Positive urine drug screen
Women of childbearing potential will have a pregnancy test performed prior to virus inoculation to exclude pregnancy and be required to use contraception throughout the study.