Mucosal and Systemic Immune Responses to Intranasal Influenza Vaccine
Research type
Research Study
Full title
Kinetics of Mucosal and Systemic Immune Responses to Intranasal Live Attenuated Influenza Vaccine (LAIV)
IRAS ID
243329
Contact name
Peter Openshaw
Contact email
Sponsor organisation
Imperial Healthcare NHS Trust
Eudract number
2018-000696-33
Duration of Study in the UK
1 years, 11 months, 26 days
Research summary
Research 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 we hope to determine correlates of efficacy and vaccine take in serum and nasal mucosal lining fluid (MLF).We wish to take 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 we shall 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. Imperial College London (ICL) has been involved in the development of novel methods of non-invasive precision mucosal sampling, including absorption of MLF from the nose by nasosorption.
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, we hope to be able 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, and to assess vaccine efficacy in large populations.
Lay summary of study results:
Healthy young adult volunteers were inoculated with a licensed nasal influenza vaccine. These volunteers were then monitored over the course of a month for the replication of the vaccine virus in the upper airway, and the immune responses that occur in response to the vaccine. No symptoms or adverse events were reported by any participant. Of the 40 inoculated participants, all completed the study schedule and antibody responses were seen in most individuals. These antibody responses were seen in both the nose and blood; interestingly these antibody responses were different between tissues. These data indicated compartmentalisation of the response to vaccine, with some responses not evident in traditional blood based measures of antibody responses.REC name
London - Camberwell St Giles Research Ethics Committee
REC reference
18/LO/0904
Date of REC Opinion
14 Jun 2018
REC opinion
Further Information Favourable Opinion