RSV Infection
Conditions
Keywords
Elderly, Human, Respiratory Syncytial Infections, RNA Virus Infections
Brief summary
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.
Detailed 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.
Interventions
BIOLOGICALRSV A Memphis 37
Subjects will be inoculated using intra-nasal drops with diluted inoculum at a given dose divided equally between the two nostrils. Dose: Good Manufacturing Practices-certified RSV Memphis 37 10(4) PFU in 1ml, 25% sucrose/Dulbecco's Modification of Eagle's Medium. Inoculations using intranasal drops will be done using a 1mL pipette with subjects supine. This will be done slowly with sufficient interval between each inoculation (2-3 minutes) to ensure maximum contact time between with the nasal and pharyngeal mucosa. Subjects will be asked not to swallow during the procedure to ensure maximal pharyngeal contact. Following inoculation, advice regarding hand hygiene will be given, subjects will be provided with alcohol hand gel and facemasks to reduce spread of virus in the environment.
Sponsors
Imperial College London
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Challenge-related Adverse Events | 180 days | To determine the safety and tolerability of experimental challenge with RSV Memphis 37, assessed by the number of participants with challenge-related adverse events. This includes any AEs deemed at least possibly related to the study challenge intervention (RSV Memphis 37). Assessed from the time of inoculation to study completion (Day 180). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Severity in RSV Infection | Day 0 to Day 14 (14 days) | This is the total symptom score for the whole 14 day period and is therefore the sum of all the scores from Day 0 to Day 14. Self-reported upper and lower respiratory and systemic symptoms by diary card. A self-completed diary card of upper respiratory tract clinical symptoms was completed on Day 0 and daily for 14 days after inoculation. A total 'upper respiratory clinical symptom score' will be derived using a four-point scale (0-3 for absent, mild, moderate and severe) for each of the following four respiratory symptoms: sneezing, nasal discharge, nasal obstruction, and sore throat, giving a maximum clinical severity score of 12 per day. |
| Nasal Viral Load Measurement in RSV Infection | Day 0 to Day 28 (28 days) | Change from baseline in viral load by qPCR of 28 days post inoculation. |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORChristopher Chiu
Imperial College London
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 15 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Age, Continuous | 66.46 years STANDARD_DEVIATION 4.16 |
| Race/Ethnicity, Customized Asian or Asian British | 1 Participants |
| Race/Ethnicity, Customized Black or Black British | 1 Participants |
| Race/Ethnicity, Customized White British | 23 Participants |
| Race/Ethnicity, Customized White Irish | 1 Participants |
| Race/Ethnicity, Customized White Other | 2 Participants |
| Region of Enrollment United Kingdom | 28 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 28 |
| other Total, other adverse events | 23 / 28 |
| serious Total, serious adverse events | 0 / 28 |
Outcome results
None listed