T-cell Diversity Following Intranasal and Intramuscular Vaccines
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional

Summary: 
      The investigators will explore in an experimental medicine healthy human model of
      immunisation, whether switching the route of sequential administration of licensed influenza
      vaccines can result in an immune response that is broader in its ability to recognise
      different substrains of influenza viruses. The investigators will do this by initially giving
      an immunisation with a nasal or an injected vaccine, and then switching subjects over to
      receive a second dose one month later (when the cellular component of immunity will have
      matured) via the opposite route (nasal->injected or injected->nasal). The investigators will
      use research assays that can map the different parts of the influenza virus that the
      vaccinated person's immune cells recognise at baseline, after the first immunisation, and
      then again after the second, to see if the breadth of the recognition has broadened to
      include new strains or virus components. Should this pilot study give an indication that the
      breadth has widened (rather than just a further boost to the same responses seen after the
      first immunisation) it will provide justification for a larger study in which statistical
      significance may be powered for observed changes.

      The study is funded by ADITEC, which is a collaborative research programme that aims to
      accelerate the development of novel and powerful immunisation technologies for the next
      generation of human vaccines.
    

Detailed description: 
      This study is an Open-label, randomised, exploratory, hypothesis generating study.

      Each participant will participate in the study for approximately two months. Recruitment aims
      to begin, on receipt of a favourable opinion from the ethics committee, in October/ November
      2015, during the flu season.

      There will be three outpatient visits during the study: Visit 1 will be screening and
      immunisation, Visit 2 will be immunisation, and Visit 3 will be an outpatient follow-up. All
      visits will take place at the Surrey Clinical Research Centre.

      Written informed consent will be obtained after a participant is informed of the nature,
      significance, implications and risks of the study and prior to the commencement of any study
      specific procedures.

      There will be two immunisations for each participant: one at Day 0 (visit 1) and the other at
      Day 28 (visit 2). After screening participants will be randomised to one of two treatment
      groups (n=15 in each group) and will receive a dose of the vaccine at the recommended dose
      level, according to the Summary of Product Characteristics, in the following orders:

      Group A: Intranasal spray at day 0 followed by intramuscular injection at day 28

      Group B: Intramuscular injection at day 0 followed by intranasal spray at day 28

      Visit 1 (Day 0): At this visit informed consent will be obtained, demographic data and
      medical history recorded. Concomitant medications will be reviewed and a symptoms-directed
      physical examination will take place. Heart rate, blood pressure and oral temperature will
      also be recorded. A pregnancy test (urine) will be conducted where indicated. Participants
      will be assessed for inclusion and exclusion criteria. At this point if the participant is
      eligible they will be randomised to group A or B. Blood samples will be taken for serum and
      PBMC and they will be given the immunisation of either the nasal spray or the intramuscular
      injection depending on which group they are in.

      Immunisation will be postponed if the person is suffering from an acute illness with an oral
      temperature ≥38.0°C on day of immunisation until the symptoms have resolved, and oral
      temperature is <38°C. Subsequent visits will be delayed by the same duration.

      Visit 2 (Day 28): At visit two, medical history will be updated and there will be a review of
      concomitant medications. A symptoms-directed physical examination will also take place. Heart
      rate, blood pressure and oral temperature will also be recorded. A pregnancy test (urine)
      will be conducted where indicated. Participants will be again be assessed for inclusion and
      exclusion criteria. Blood samples will be taken for serum and PBMC and they will be given the
      immunisation of either the nasal spray or the intramuscular injection depending on which
      group they are in

      Immunisation will be postponed if the person is suffering from an acute illness with an oral
      temperature ≥38.0°C on day of immunisation until the symptoms have resolved, and oral
      temperature is <38°C.

      A visit window of -3 days or +7 days is acceptable for Visit 2 but should be avoided wherever
      possible and used only in a situation where a sample would otherwise be lost. Visit 3 should
      be rescheduled to maintain 28 days between visits.

      Visit 3 (Day 56): At visit 3 there will be a review on concomitant medications and blood
      samples will be taken for serum and PBMC.

      A visit window of -3 and +14 days is acceptable for Visit 3 but should be avoided wherever
      possible and used only in a situation where a sample would otherwise be lost. If participants
      cannot attend within this window then samples should be collected on the earliest date
      possible AFTER the expected visit window. These samples may be tested but will not be per
      protocol.
    

Intervention name(s): Fluenz Tetra; Fluarix Tetra
Intervention type(s): Biological; Biological
Intervention description(s): Intranasal spray, 0.2 ml dose; Intramuscular injection, 0.5 ml dose
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)