Nasal and Systemic Immune Responses to Nasal Influenza Vaccine (Flu-M3)
Primary Purpose
Influenza, Vaccine Virus Shedding
Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Live attenuated influenza vaccine
Vehicle control
Sponsored by
About this trial
This is an interventional basic science trial for Influenza focused on measuring influenza, vaccine, virus, antibody, cytokine, respiratory
Eligibility 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
Sites / Locations
- Imperial Clinical Respiratory Research Unit
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Live attenuated influenza vaccine
Mucosal immune stability cohort
Arm Description
Participants receiving live attenuated influenza vaccine (LAIV)
Participants receiving a vehicle control nasal challenge
Outcomes
Primary Outcome Measures
Number of Participants Shedding Each Vaccine Virus Measured by qPCR of Nasosorption Samples
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
Number of Participants With >2-fold Rise in Mucosal and/or Serum Antibody Titre Against Each Vaccine Virus Haemagglutinin Antigens
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.
Full Information
NCT ID
NCT04110366
First Posted
September 9, 2019
Last Updated
November 1, 2021
Sponsor
Imperial College Healthcare NHS Trust
1. Study Identification
Unique Protocol Identification Number
NCT04110366
Brief Title
Nasal and Systemic Immune Responses to Nasal Influenza Vaccine
Acronym
Flu-M3
Official Title
Kinetics of Mucosal and Systemic Immune Responses to Intranasal Live Attenuated Influenza Vaccine (LAIV)
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
June 14, 2018 (Actual)
Primary Completion Date
April 4, 2019 (Actual)
Study Completion Date
May 29, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Imperial College Healthcare NHS Trust
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, Vaccine Virus Shedding
Keywords
influenza, vaccine, virus, antibody, cytokine, respiratory
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Live attenuated influenza vaccine
Arm Type
Experimental
Arm Description
Participants receiving live attenuated influenza vaccine (LAIV)
Arm Title
Mucosal immune stability cohort
Arm Type
Experimental
Arm Description
Participants receiving a vehicle control nasal challenge
Intervention Type
Biological
Intervention Name(s)
Live attenuated influenza vaccine
Other Intervention Name(s)
Fluenz
Intervention Description
Vaccination with live attenuated influenza vaccine (LAIV)
Intervention Type
Other
Intervention Name(s)
Vehicle control
Intervention Description
Vehicle control nasal challenge
Primary Outcome Measure Information:
Title
Number of Participants Shedding Each Vaccine Virus Measured by qPCR of Nasosorption Samples
Description
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.
Time Frame
1-7 days post vaccination
Secondary Outcome Measure Information:
Title
Number of Participants With >2-fold Rise in Mucosal and/or Serum Antibody Titre Against Each Vaccine Virus Haemagglutinin Antigens
Description
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.
Time Frame
28 days post vaccination
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter J Openshaw, PhD
Organizational Affiliation
Imperial College London
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Trevor T Hansel, PhD
Organizational Affiliation
Imperial College London
Official's Role
Study Director
Facility Information:
Facility Name
Imperial Clinical Respiratory Research Unit
City
London
ZIP/Postal Code
W2 1PG
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing Time Frame
From June 2020 onward, no set end date
IPD Sharing Access Criteria
PI discretion
Learn more about this trial
Nasal and Systemic Immune Responses to Nasal Influenza Vaccine
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