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Nasal and Systemic Immune Responses to Nasal Influenza Vaccine (Flu-M3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04110366
Recruitment Status : Completed
First Posted : October 1, 2019
Results First Posted : December 6, 2021
Last Update Posted : December 6, 2021
Sponsor:
Information provided by (Responsible Party):
Imperial College Healthcare NHS Trust

Study Description
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Brief Summary:
Intranasal live attenuated influenza vaccine (LAIV; trade name FluMist/Fluenz-Tetra, manufactured by AstraZeneca/Medimmune) is the standard influenza vaccine given to children aged 2-17 years of age in the UK. It is also licensed to be given to adults up to the age of 49 years in the USA. The systems biology of the human blood response to influenza vaccines has been studied in great detail, but there is a paramount need to study innate and specific, soluble and cellular immune responses at the nasal mucosal site of influenza infection. In this way this study aims to determine correlates of efficacy and vaccine take in serum and nasal mucosal lining fluid (MLF).

Condition or disease Intervention/treatment Phase
Influenza Vaccine Virus Shedding Biological: Live attenuated influenza vaccine Other: Vehicle control Not Applicable

Detailed Description:

This study will collect serial samples prior to vaccination and at intervals up to day 28 post-vaccination to establish the kinetics of the nasal mucosal and blood systemic response to LAIV in young adults aged 18-30 years (n=40). In the nose the investigators will measure viral load, soluble mediators of inflammation and antibodies (humoral immunity) in mucosal lining fluid; while cellular immune responses and serology will be assessed in blood samples. Investigators at Imperial College London (ICL) have been involved in the development of novel methods of non-invasive precision mucosal sampling, including absorption of MLF from the nose by nasosorption. The investigators have also developed assays for influenza-specific IgA by ELISA, and aim to compare this assay against a repertoire of serological assays in patients after LAIV administration.

The study will precisely assess mucosal and systemic immune responses to the LAIV nasal vaccine.

The primary endpoint will be based on nasal mucosal levels of IgA and IgG antibodies to the 4 constituent viral subtypes in LAIV: measured by ELISA and multiplex immunoassay (Mesoscale Diagnostics) and expressed as seroconversion rates, geometric mean titre (GMT) changes, and geometric mean fold rises (GMFR). The secondary endpoints will be: (1) haemagglutination inhibition (HAI) assay titres measured in serum and the nose, (2) influenza pseudotype neutralisation by antibodies in serum and the nose, (3) nasal cytokine and chemokine levels as measured by immunoassay and (4) nasal viral load quantified by qPCR.

It is thought that the immune response to LAIV in an individual is mediated by a combination of mucosal and systemic factors, involving innate and specific mechanisms that have different kinetics, and various cell types. By understanding the molecular and cellular basis of the nasal mucosal response to LAIV, the investigators hope to identify key molecular signatures and biomarkers associated with LAIV responses, and to assess protective pathways that could be stimulated by novel vaccines. The nasal vaccine challenge model could be used to test other new vaccines, and proceed to rational development of improved vaccines for influenza and other diseases. Furthermore nasal mucosal methods could be used in the clinic to identify subjects who have responded poorly to vaccines, or to assess vaccine efficacy in large populations.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Kinetics of Mucosal and Systemic Immune Responses to Intranasal Live Attenuated Influenza Vaccine (LAIV)
Actual Study Start Date : June 14, 2018
Actual Primary Completion Date : April 4, 2019
Actual Study Completion Date : May 29, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Live attenuated influenza vaccine
Participants receiving live attenuated influenza vaccine (LAIV)
 Biological: Live attenuated influenza vaccine
Vaccination with live attenuated influenza vaccine (LAIV)
Other Name: Fluenz
Experimental: Mucosal immune stability cohort
Participants receiving a vehicle control nasal challenge
 Other: Vehicle control
Vehicle control nasal challenge


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants Shedding Each Vaccine Virus Measured by qPCR of Nasosorption Samples [ Time Frame: 1-7 days post vaccination ]
    Vaccine virus shedding in nasosorption samples collected between 1-7 days post-vaccination and quantified using multiplex qPCR assay measures in the LAIV vaccine recipient cohort.


Secondary Outcome Measures :
  1. Number of Participants With >2-fold Rise in Mucosal and/or Serum Antibody Titre Against Each Vaccine Virus Haemagglutinin Antigens [ Time Frame: 28 days post vaccination ]
    Vaccine specific antibody (IgG and IgA) titres in serum and/or respiratory secretions (nasosorption and nasal wash) measured using endpoint titre and arbitrary unit level immunoassay measurements of samples collected from the n=40 LAIV vaccine recipient arm.


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 30 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Capacity to provide written informed consent
  • Aged 18-30 years (inclusive)
  • Fluent English speaker

Exclusion Criteria:

  • Current involvement in another study unless observational or in follow-up phase (non-interventional)
  • Received any influenza vaccine over the last 2 years
  • Egg allergy
  • Previous significant adverse reaction to any vaccination/immunisation
  • Current regular (daily) smoker
  • Pregnant
  • Any medication that may affect the immune system (e.g. steroids)
  • Taking regular acetylsalicylic acid (aspirin)
  • Unable to give informed consent
  • Current acute severe febrile illness
  • Taking long term antibiotics
  • Clinically diagnosed influenza in the last 2 years
  • Any long-term health problem with heart disease, lung disease (including asthma), kidney disease, neurologic disease, liver disease, metabolic disease (e.g. diabetes) or anemia or another blood disorder
  • Use of drugs for the treatment of rheumatoid arthritis, Crohn's disease, or psoriasis or anticancer drugs; or radiation treatments
  • History of Guillain-Barre syndrome
  • Live with or expect to have close contact with a person whose immune system is severely compromised and who must be in protective isolation (e.g., an isolation room of a bone marrow transplant unit)
  • Received any other vaccinations in the past 4 weeks
Contacts and Locations
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Information from the National Library of Medicine

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): NCT04110366


Locations
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United Kingdom
Imperial Clinical Respiratory Research Unit
London, United Kingdom, W2 1PG
Sponsors and Collaborators
Imperial College Healthcare NHS Trust
Investigators
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Principal Investigator: Peter J Openshaw, PhD Imperial College London
Study Director: Trevor T Hansel, PhD Imperial College London
  Study Documents (Full-Text)

Documents provided by Imperial College Healthcare NHS Trust:
Study Protocol and Statistical Analysis Plan  [PDF] March 7, 2018

More Information
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Responsible Party: Imperial College Healthcare NHS Trust
ClinicalTrials.gov Identifier: NCT04110366    
Other Study ID Numbers: 18/LO/0904
First Posted: October 1, 2019    Key Record Dates
Results First Posted: December 6, 2021
Last Update Posted: December 6, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD sharing is available upon request to the study PI; but access is offered at the discretion of the PI and requests are not guaranteed access. All access will require ethical approval.
Supporting Materials: Study Protocol
Clinical Study Report (CSR)
Analytic Code
Time Frame: From June 2020 onward, no set end date
Access Criteria: PI discretion

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Imperial College Healthcare NHS Trust:
influenza
vaccine
virus
 antibody
cytokine
respiratory
Additional relevant MeSH terms:
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Influenza, Human
Respiratory Tract Infections
Infections
Orthomyxoviridae Infections
 RNA Virus Infections
Virus Diseases
Respiratory Tract Diseases