Nasal and Systemic Immune Responses to Nasal Influenza Vaccine
Condition: Influenza; Vaccine Virus Shedding
MeSH terms: Influenza, Human
Study type: Interventional

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.
    

Intervention name(s): Live attenuated influenza vaccine; Vehicle control
Intervention type(s): Biological; Other
Intervention description(s): Vaccination with live attenuated influenza vaccine (LAIV); Vehicle control nasal challenge
Other intervention name(s): Fluenz
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: influenza; vaccine; virus; antibody; cytokine; respiratory