Cell Mediated Immunity Against RSV and Influenza in a Human Experimental Challenge

NCT02755948 | Completed Results DMC

• 2 other identifiers: 13SM036511/LO/1826
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Respiratory Syncytial Virus Infections; Influenza, Human

Keywords

Influenza; Respiratory Syncytial Virus Infections; RSV A Memphis 37

Outcome Measures

Primary Outcomes (1)

• Total Symptom Score

  Total Symptom Score in infected versus uninfected participants by Jackson's criteria. Eight symptoms were evaluated in the symptom diary: nasal discharge, nasal congestion, sneezing, cough, sore throat, headache, feverishness and fatigue. Subjects were asked to score each symptom 0 (absent), 1 (mild), 2 (moderate), 3 (severe). A clinical cold was defined as 2 out of 3 of: a cumulative 14-day symptom score of ≥14; a subjective feeling of a cold; nasal discharge for ≥3 days. Symptoms were evaluated over a longer period than in Jackson's original description to account for an anticipated slower onset and longer duration of illness with RSV compared with rhinovirus. Maximum cumulative symptom score is therefore 336.

  14 days

Secondary Outcomes (4)

• Frequency of T Cells in Blood by Flow Cytometry

  6 months

• Frequency of T Cells in Respiratory Tract by Flow Cytometry

  6 months

• Viral Load

  28 days

• Frequency of T Cells in Blood by Enzyme-linked Immunospot (ELISpot)

  6 months

Study Arms (3)

RSV A Memphis 37

EXPERIMENTAL

Participants will be inoculated with RSV Memphis 37 virus.

Biological: RSV A Memphis 37

Influenza A/California/04/2009-like (H1N1)

EXPERIMENTAL

Participants will be inoculated with Influenza A/California/04/2009-like (H1N1).

Biological: Influenza A/California/04/2009-likw (H1N1)

Influenza A/Belgium/4217/2015 (H3N2)

EXPERIMENTAL

Participants will be inoculated with Influenza A/Belgium/4217/2015 (H3N2).

Biological: Influenza A/Belgium/4217/2015 (H3N2)

Interventions

RSV A Memphis 37 BIOLOGICAL

Good Manufacturing Practices-certified RSV Memphis 37 10(4) PFU in 1 mL 25% sucrose/DMEM delivered by intranasal drops

RSV A Memphis 37

Influenza A/California/04/2009-likw (H1N1) BIOLOGICAL

Good Manufacturing Practices-certified Influenza A/California/04/09 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops

Influenza A/California/04/2009-like (H1N1)

Influenza A/Belgium/4217/2015 (H3N2) BIOLOGICAL

Good Manufacturing Practices-certified Influenza A/Belgium/4217/2015 (H3N2) 3.5x10\^6 TCID50 in 1 mL in DPBS delivered by intranasal drops

Influenza A/Belgium/4217/2015 (H3N2)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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 3 months
• Acute upper respiratory infection (URI 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
• Any ECG abnormality
• 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

Sponsors & Collaborators

• Imperial College London: lead
• Medical Research Council: collaborator
• Wellcome Trust: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (1)

National Heart and Lung Institute, Imperial College London

London, W2 1PG, United Kingdom

Location

Related Publications (4)

• Jozwik A, Habibi MS, Paras A, Zhu J, Guvenel A, Dhariwal J, Almond M, Wong EHC, Sykes A, Maybeno M, Del Rosario J, Trujillo-Torralbo MB, Mallia P, Sidney J, Peters B, Kon OM, Sette A, Johnston SL, Openshaw PJ, Chiu C. RSV-specific airway resident memory CD8+ T cells and differential disease severity after experimental human infection. Nat Commun. 2015 Dec 21;6:10224. doi: 10.1038/ncomms10224.

  PMID: 26687547 RESULT

• Currie SM, Gwyer Findlay E, McFarlane AJ, Fitch PM, Bottcher B, Colegrave N, Paras A, Jozwik A, Chiu C, Schwarze J, Davidson DJ. Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans. J Immunol. 2016 Mar 15;196(6):2699-710. doi: 10.4049/jimmunol.1502478. Epub 2016 Feb 12.

  PMID: 26873992 RESULT

• Paterson S, Kar S, Ung SK, Gardener Z, Bergstrom E, Ascough S, Kalyan M, Zyla J, Maertzdorf J, Mollenkopf HJ, Weiner J, Jozwik A, Jarvis H, Jha A, Nicholson BP, Veldman T, Woods CW, Mallia P, Kon OM, Kaufmann SHE, Openshaw PJ, Chiu C. Innate-like Gene Expression of Lung-Resident Memory CD8+ T Cells during Experimental Human Influenza: A Clinical Study. Am J Respir Crit Care Med. 2021 Oct 1;204(7):826-841. doi: 10.1164/rccm.202103-0620OC.

  PMID: 34256007 DERIVED

• Guvenel A, Jozwik A, Ascough S, Ung SK, Paterson S, Kalyan M, Gardener Z, Bergstrom E, Kar S, Habibi MS, Paras A, Zhu J, Park M, Dhariwal J, Almond M, Wong EH, Sykes A, Del Rosario J, Trujillo-Torralbo MB, Mallia P, Sidney J, Peters B, Kon OM, Sette A, Johnston SL, Openshaw PJ, Chiu C. Epitope-specific airway-resident CD4+ T cell dynamics during experimental human RSV infection. J Clin Invest. 2020 Jan 2;130(1):523-538. doi: 10.1172/JCI131696.

  PMID: 31815739 DERIVED

MeSH Terms

Conditions

Respiratory Syncytial Virus Infections; Influenza, Human

Condition Hierarchy (Ancestors)

Pneumovirus Infections; Paramyxoviridae Infections; Mononegavirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Orthomyxoviridae Infections; Respiratory Tract Diseases

Results Point of Contact

• Title: Professor Christopher Chiu
• Organization: Imperial College London

c.chiu@imperial.ac.uk

(0)20 8383 2301

Study Officials

• Christopher Chiu, BMBCh PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: GMP influenza A/California/04/2009-like (H1N1); influenza A/Belgium/4217/2015 (H3N2); or RSV Memphis 37 virus strains will be used for experimental infection of volunteers.

Study Record Dates

• First Submitted: April 11, 2016
• First Posted: April 29, 2016
• Study Start: April 1, 2012
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: December 6, 2024
• Results First Posted: December 6, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)