ADITEC FLU 2 STUDY: Understanding the Genetics Basis for Immune Responses to Flu Vaccines in Children and Adults
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 2

Summary: 
      Influenza infection is related to significant morbidity and mortality in children. The
      trivalent inactive vaccine (TIV) has been documented to have poor immunogenicity in children
      and the live attenuated influenza vaccine (ATIV) although proven to have more efficacy is
      unable to be administered to children under 2 years old. The MF59 adjuvanted influenza
      vaccine as proven efficacy on reducing the rates of laboratory confirmed influenza, including
      in children.

      The study aims to assess early gene transcriptional responses to priming and boosting with
      MF59-ATIV in children aged 13-24 months and adults aged 18 - 65 years, and to establish
      correlations with haemagglutination inhibition (HAI) titers. It will be an open label study
      with 90 healthy children allocated to 3 groups (groups 1, 2 and 3) and 30 healthy adults
      allocated to group 4.
    

Detailed description: 
      Influenza infection is related to significant morbidity and mortality in children. The
      commonly used trivalent inactive influenza vaccine (TIV) has been documented to have poor
      immunogenicity in children, particularly in those less than 2 years old. The live attenuated
      influenza vaccine (LAIV) has shown improved efficacy compared to TIV, however LAIV is unable
      to be administered to children under 2 years old and those with contraindications, hence an
      effective alternative is required.

      The focus toward adjuvanted influenza vaccines for children, particularly the MF59 adjuvant,
      has shown promising results in relation to safety and efficacy. This study aims to further
      explore the MF59 adjuvanted influenza vaccine from a gene expression perspective using a
      systems biology approach and relate these findings to innate immune responses, immunogenicity
      and reactogenicity.

      The MF-59 adjuvant was approved for human use in 1997 and was studied initially in the
      elderly and more recently in children as young as 6 months. MF59-ATIV (Fluad®, Gripguard®
      (France) and Chiromas® (Spain)) is approved in Europe for adults aged 65 years and over and
      has been administered to over 5000 children in clinical trials.

      In a recent large study with over 4000 children aged 6 months to 72 months, MF59-ATIV
      significantly reduced rates of laboratory-confirmed influenza with an absolute efficacy of
      86%, demonstrating this vaccine to be an effective option for vaccinating children less than
      2 years old unable to have the live attenuated vaccine. Unpublished data from the ADITEC Flu
      pilot study conducted in 2012 (EudraCT Number: 2012-002443-26, Ethics Ref: OxREC C
      12/SC/0407); a phase 2, randomised, open label study, also demonstrated increased
      immunogenicity and a relatively similar reactogenicity profile following ATIV immunisation
      compared to TIV.

      This study will use a systems biology approach to identify early gene signatures that relate
      to common innate and adaptive immune pathways following priming and boosting with ATIV, and
      to correlate these results with HAI response in children and adults.The systems biology
      approach has been used previously in vaccine research to identify gene module expression,
      including studies focusing on description of gene expression following the yellow fever
      vaccine (YF-17D), LAIV and TIV in adults. The study aims to assess early gene transcriptional
      responses to priming and boosting with MF59-ATIV in children aged 13-24 months and adults
      aged 18 - 65 years, and to establish correlations with HAI titers. It will be an open label
      study with 90 healthy children allocated to 3 groups (groups 1, 2 and 3) and 30 healthy
      adults allocated to group 4. Each participant will have an initial visit where screening will
      be completed and informed consent taken. The participant will then be enrolled and allocated
      a study participant number at this time. This initial visit ('Screening visit') will occur
      within the 56 days prior to the first ATIV immunisation. Group allocation will occur at or
      after the screening visit. Each child will receive 2 doses of ATIV and adults will receive 1
      dose. ATIV is not currently licensed for children, and looking to previous studies, ATIV has
      been given to children less than 36 months as two 0.25 ml injections 4 weeks apart, and we
      will follow that immunisation schedule in this study. The timing of blood samples to be taken
      during the study will differ for each group in order to minimise number of blood collections
      per child but still enable assessment of gene expression and immune response at multiple time
      points.
    

Intervention name(s): MF59 - ATIV
Intervention type(s): Biological
Intervention description(s): All child participants will receive 2 doses of the MF59-ATIV, with the doses separated by 28 days.
Adult participants will receive one dose of MF59-ATIV.
Other intervention name(s): Fluad vaccine
Intervention MeSH terms: Vaccines
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention