InfluenzaFlu-M3NCT04110366
Nasal and Systemic Immune Responses to Nasal Influenza Vaccine
A study testing Live attenuated influenza vaccine in people with Influenza and Vaccine Virus Shedding, run by Imperial College Healthcare NHS Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Influenza, Vaccine Virus Shedding
- What is being tested?
- Live attenuated influenza vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 14 Jun 2018to 29 May 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Capacity to provide written informed consent
- Aged 18-30 years (inclusive)
- Fluent English speaker
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial Clinical Respiratory Research Unit
London, W2 1PG
About this study
Official title: Kinetics of Mucosal and Systemic Immune Responses to Intranasal Live Attenuated Influenza Vaccine (LAIV)
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).
Read the 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.
- Conditions
- Influenza, Vaccine Virus Shedding
- Being tested
- Live attenuated influenza vaccine, Vehicle control
- Keywords
- influenza, vaccine, virus, antibody, cytokine, respiratory
- Medical subject headings
- Influenza, Human, Virus Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Live attenuated influenza vaccineBiological
Also called Fluenz
Vaccination with live attenuated influenza vaccine (LAIV)
Vehicle controlOther
Vehicle control nasal challenge
| Study group | Role | What they receive |
|---|---|---|
| Live attenuated influenza vaccine | Experimental | Participants receiving live attenuated influenza vaccine (LAIV) Receives: Biological: Live attenuated influenza vaccine |
| Mucosal immune stability cohort | Experimental | Participants receiving a vehicle control nasal challenge Receives: Other: Vehicle control |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1-7 days post vaccination
Secondary outcomes (1)
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.
Measured: 28 days post vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2019
- Study start14 Jun 2018
- Primary completion4 Apr 2019
- Study completion29 May 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College Healthcare NHS Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter J Openshaw, PhD, Principal investigator, Imperial College LondonTrevor T Hansel, PhD, Study director, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04110366
- Sponsor's protocol ID
- 18/LO/0904
- Acronym
- Flu-M3
- Status last verified
- Nov 2021
- First submitted
- 9 Sep 2019
- Last updated
- 6 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Thwaites RS, Uruchurtu ASS, Negri VA, Cole ME, Singh N, Poshai N, Jackson D, Hoschler K, Baker T, Scott IC, Ros XR, Cohen ES, Zambon M, Pollock KM, Hansel TT, Openshaw PJM. Early mucosal events promote distinct mucosal and systemic antibody responses to live attenuated influenza vaccine. Nat Commun. 2023 Dec 5;14(1):8053. doi: 10.1038/s41467-023-43842-7.
PubMed 38052824
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Kinetics of Mucosal and Systemic Immune Responses to Intranasal Live Attenuated Influenza Vaccine (LAIV)
- ClinicalTrials.gov ID
- NCT04110366
- Acronym / sponsor ID
- Flu-M3 / 18/LO/0904
- Conditions
- Influenza, Vaccine Virus Shedding
- Keywords
- influenza, vaccine, virus, antibody, cytokine, respiratory
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Imperial College Healthcare NHS TrustUniversity, hospital or other
- Study start
- 14 Jun 2018 (actual)
- Primary completion
- 4 Apr 2019 (actual)
- Study completion
- 29 May 2020 (actual)
- First posted
- 1 Oct 2019 (actual)
- Results
- Posted 6 Dec 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Live attenuated influenza vaccine | Experimental | Biological: Live attenuated influenza vaccineParticipants receiving live attenuated influenza vaccine (LAIV) |
| Mucosal immune stability cohort | Experimental | Other: Vehicle controlParticipants receiving a vehicle control nasal challenge |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Capacity to provide written informed consent
- Aged 18-30 years (inclusive)
- Fluent English speaker
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Live attenuated influenza vaccineAlso: FluenzVaccination with live attenuated influenza vaccine (LAIV) | Biological | Live attenuated influenza vaccine |
| Vehicle controlVehicle control nasal challenge | Other | Mucosal immune stability cohort |
Primary outcome
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.
1 secondary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38052824Thwaites RS, Uruchurtu ASS, Negri VA, Cole ME, Singh N, Poshai N, Jackson D, Hoschler K, Baker T, Scott IC, Ros XR, Cohen ES, Zambon M, Pollock KM, Hansel TT, Openshaw PJM. Early mucosal events promote distinct mucosal and systemic antibody responses to live attenuated influenza vaccine. Nat Commun. 2023 Dec 5;14(1):8053. doi: 10.1038/s41467-023-43842-7.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter J Openshaw, PhD principal investigator
Imperial College London
Trevor T Hansel, PhD study director
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Live attenuated influenza vaccine in people with Influenza and Vaccine Virus Shedding, run by Imperial College Healthcare NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Dec 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Shedding Each Vaccine Virus Measured by qPCR of Nasosorption Samples (time frame: 1-7 days post vaccination). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04110366, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2021; AzTrials last refreshed its copy on 7 Nov 2026.