A Study of Protective Immunity Against RSV and Influenza in Experimental Human Challenge of Volunteers

  • STATUS
    Recruiting
  • End date
    Mar 29, 2023
  • participants needed
    120
  • sponsor
    Imperial College London
Updated on 12 February 2022
Accepts healthy volunteers

Summary

Respiratory viruses including influenza and respiratory syncytial virus (RSV) are among the most important causes of severe disease globally, infecting everyone repeatedly throughout life. Understanding of how to prevent infection is incomplete but boosting immunity with vaccines remains the best strategy. T cells have been shown in animals to be essential for clearing respiratory viral infection and are likely to be helpful if stimulated by vaccines. However, where these cells originate from and how they develop in the human lung are still unclear. The investigators will inoculate volunteers with influenza or RSV to examine the relationship between T cells in their blood and lungs and the outcome of infection. By tracking these specialised cells, the investigators aim to develop a better understanding of how they are generated in order to harness them with future vaccines.

Description

Influenza and Respiratory Syncytial Virus (RSV) are the two most common causes of severe viral respiratory tract infection. Seasonal influenza has an overall incidence of 10-20% per annum with frequent complications, and the annual mortality in the USA has been estimated at up to 9.9 deaths per 100,000. According to World Health Organization (WHO) estimates, RSV causes around 64 million infections per annum and 160,000 deaths. It is the leading cause of severe respiratory illness in young children (associated with severe infant wheezing illness) and is also a significant problem in susceptible adults (including the elderly and those with airways disease) in whom RSV is responsible for around 22% of winter respiratory illnesses with a case fatality rate of 2-8%. No vaccines or specific antivirals are available for RSV and those licensed for influenza remain suboptimal. Further understanding of the human immune response to these viruses particularly in the context of the respiratory tract is therefore essential. Experimental human infection studies have the advantage of studying these pathogens in their natural host with the capacity to sample different anatomical sites intensively. Thus the investigators aim to use these models in helping to test vaccines and therapeutics as well as providing critical information on immunity and pathogenesis.

The investigators will use previously characterised Good Manufacturing Practices-certified RSV and influenza viruses derived from recent clinical isolates to investigate the response to infection in healthy adult volunteers. Subjects will be recruited via advertisement and screened at Imperial College London. Healthy individuals will be enrolled in the study and undergo baseline investigations including sampling from blood, upper and lower respiratory tract. They will then be inoculated with RSV or influenza by intranasal drops and quarantined for 10 days. During this time, they will have further blood and respiratory sampling. After the 10 day isolation period, they will be discharged and followed up for up to 6 months post-infection.

These samples will undergo analysis for antibody, B and T cell responses to correlate with outcome of inoculation, which may include no infection, asymptomatic or symptomatic infection. Thus the investigators will infer the role of immune correlates in protection against infection or symptomatic disease.

Details
Condition Respiratory Syncytial Virus Infections, Influenza, Human
Treatment RSV A Memphis 37, Influenza A/California/04/2009
Clinical Study IdentifierNCT02755948
SponsorImperial College London
Last Modified on12 February 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Healthy persons aged 18 to 55 years, able to give informed consent

Exclusion Criteria

Chronic respiratory disease (asthma, chronic obstructive pulmonary disease, rhinitis, sinusitis) in adulthood
Inhaled bronchodilator or steroid use within the last 12 months
Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within the last 6 months
Acute upper respiratory infection or sinusitis in the past 6 weeks
Smoking in the past 6 months OR >5 pack-year lifetime history
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, the elderly (>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 immunoglobulin A 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
Pregnant or breastfeeding women
Positive urine drug screen
Detectable baseline haemagglutination inhibition titres against influenza challenge strains
Influenza arm only: history of hypersensitivity to eggs, egg proteins, gentamicin, gelatin or arginine, or with life-threatening reactions to previous influenza vaccinations
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Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

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