- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04110366
Nasal and Systemic Immune Responses to Nasal Influenza Vaccine (Flu-M3)
Kinetics of Mucosal and Systemic Immune Responses to Intranasal Live Attenuated Influenza Vaccine (LAIV)
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
London, United Kingdom, W2 1PG
- Imperial Clinical Respiratory Research Unit
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: BASIC_SCIENCE
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Live attenuated influenza vaccine
Participants receiving live attenuated influenza vaccine (LAIV)
|
Vaccination with live attenuated influenza vaccine (LAIV)
Other Names:
|
EXPERIMENTAL: Mucosal immune stability cohort
Participants receiving a vehicle control nasal challenge
|
Vehicle control nasal challenge
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
1-7 days post vaccination
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
28 days post vaccination
|
Collaborators and Investigators
Investigators
- Principal Investigator: Peter J Openshaw, PhD, Imperial College London
- Study Director: Trevor T Hansel, PhD, Imperial College London
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 18/LO/0904
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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