A Study of Protective Immunity Against RSV and Influenza in Experimental Human Challenge of Volunteers
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|ClinicalTrials.gov Identifier: NCT02755948|
Recruitment Status : Terminated (Study objectives have been met.)
First Posted : April 29, 2016
Last Update Posted : June 29, 2022
|Condition or disease||Intervention/treatment||Phase|
|Respiratory Syncytial Virus Infections Influenza, Human||Biological: RSV A Memphis 37 Biological: Influenza A/California/04/2009||Not Applicable|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||95 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Cell Mediated Immunity Against RSV and Influenza in a Human Experimental Challenge|
|Actual Study Start Date :||April 2012|
|Actual Primary Completion Date :||February 1, 2020|
|Actual Study Completion Date :||February 1, 2020|
Experimental: RSV A Memphis 37
Half the participants will be inoculated with RSV Memphis 37 10(4) plaque forming units (PFU) in 1 milliliter (mL) 25% sucrose/Dulbecco's Modification of Eagle's Medium (DMEM) delivered by intranasal drops. They will then be monitored as in-patients for 10 days with daily clinical assessment and blood and respiratory tract sampling. Following discharge, they will be followed up for up to 6 months post-inoculation.
Biological: RSV A Memphis 37
Good Manufacturing Practices-certified RSV Memphis 37 10(4) PFU in 1 mL 25% sucrose/DMEM delivered by intranasal drops
Experimental: Influenza A/California/04/2009
Half the participants will be inoculated with Influenza A/California/04/09 3.5x10(4) tissue culture infective dose 50% (TCID50) in 1 mL in Dulbecco's phosphate buffered saline (DPBS) delivered by intranasal drops. They will then be monitored as in-patients for 10 days with daily clinical assessment and blood and respiratory tract sampling. Following discharge, they will be followed up for up to 6 months post-inoculation.
Biological: Influenza A/California/04/2009
Good Manufacturing Practices-certified Influenza A/California/04/09 3.5x10(4) TCID50 in 1 mL in DPBS delivered by intranasal drops
- Symptoms [ Time Frame: 28 days ]Self-reported upper and lower respiratory and systemic symptoms by diary card
- Frequency of T cells in blood and respiratory tract by flow cytometry [ Time Frame: 6 months ]Frequency of T cells in blood and respiratory tract by flow cytometry as a proportion of live lymphocytes
- Frequency of T cells in blood and respiratory tract by enzyme-linked immunospot (ELISpot) [ Time Frame: 6 months ]Frequency of antigen-specific T cells in blood and respiratory tract by enzyme-linked immunospot (ELISpot) as a proportion of mononuclear cells
- Virus-specific serum plaque reduction neutralization titer [ Time Frame: 6 months ]Antibody responses to infection in blood and respiratory tract by plaque reduction neutralisation assay
- Virus-specific antibody geometric mean titer [ Time Frame: 6 months ]Antibody responses to infection in blood and respiratory tract by enzyme-linked immunoassay (ELISA) as a proportion of mononuclear cells
- Frequency of B cells in blood and respiratory tract by flow cytometry [ Time Frame: 6 months ]Frequency of virus-specific B cells by flow cytometry as a proportion of live lymphocytes
- Frequency of B cells in blood and respiratory tract by ELISpot [ Time Frame: 6 months ]Frequency of virus-specific B cells by ELISpot
- Viral load [ Time Frame: 28 days ]Nasal wash viral load by quantitative polymerase chain reaction (qPCR)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02755948
|National Heart and Lung Institute, Imperial College London|
|London, United Kingdom, W2 1PG|
|Principal Investigator:||Christopher Chiu, BMBCh PhD||Imperial College London|