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
|Condition or disease||Intervention/treatment||Phase|
|Influenza Vaccine Virus Shedding||Biological: Live attenuated influenza vaccine Other: Vehicle control||Not Applicable|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||48 participants|
|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|
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
- 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.
- 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.
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
|Imperial Clinical Respiratory Research Unit|
|London, United Kingdom, W2 1PG|
|Principal Investigator:||Peter J Openshaw, PhD||Imperial College London|
|Study Director:||Trevor T Hansel, PhD||Imperial College London|