Routes of Immunization and Flu Immune Responses
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The project aims to evaluate the impact of skin routes of immunization (transcutaneous and
      intradermal vs intramuscular) on cellular and humoral responses to seasonal influenza
      vaccination in adults (18-45 years old).
    

Detailed description: 
      New approaches addressing intradermal (ID) and transcutaneous (TC) routes of immunization
      have been developed over the past few years and have brought novel insight in quality and
      efficacy of the immune response. Indeed, compared to the muscular tissue widely used for
      vaccination, the skin is particularly rich in antigen presenting cells. Our recent works show
      that penetration of vaccine compounds into the hair follicular ducts surrounded by Langerhans
      cells induces potent cellular immunity in contrast to the intra-muscular immunization. Our
      results also suggest that differential targeting of epidermal Langerhans cells (by TC route)
      or dermal dendritic cells (by ID route) could modulate the intensity and quality of the
      immune response to vaccine.

      The aim of this study is to evaluate the immune response to a seasonal influenza vaccine when
      administrated byTC (hair follicular targeting needle-free method), ID (micro-needle
      injection) and IM (conventional intramuscular injection) routes of immunization. Along with
      our previous pre-clinical and clinical studies, here we hypothesize that differential
      targeting of epidermis or dermis antigen-presenting cells will have a differential impact on
      the cellular and humoral immune responses to Influenza vaccine.

      Objectives:

      We will conduct a phase I/II clinical trials on 60 healthy volunteers to compare TC and ID
      routes of immunization to the conventional intramuscular (IM) vaccination. The impact of
      these routes on cellular and humoral immune responses to seasonal influenza vaccine will be
      assessed at baseline, day 21 (effector phase) and month 5 (memory phase) after vaccination.

      Outcomes:

      Using the seasonal Influenza vaccine as an example of conventional vaccine, this study will
      evaluate and compare the efficacy ofTC, ID and IMroutes of immunization to induce cellular
      responses at day 21 and memory responses at month 5 phases. The generation and maintenance of
      Flu specific and neutralizing antibodies will be measured by Haemagglutination Inhibition and
      microneutralization assays.Moreover, safety and tolerance to each vaccination methods will be
      evaluated as well as inflammation and innate immune response induced at day 1 after
      vaccination.

      Addressing innovative skin routes of immunization, this study represents an essential step to
      move forward in the development of new vaccination strategies. These results will have an
      important impact on the amelioration of vaccine efficacy and less invasive method of
      immunization.
    

Intervention name(s): INTANZA® 15; Vaxigrip®; INTANZA® 15 T
Intervention type(s): Biological; Biological; Biological
Intervention description(s): intradermal vaccination; Intramuscular vaccination; transcutaneous vaccination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Keywords: Intradermal; transcutaneous; influenza; routes of vaccination; T cell responses; humoral responses; skin; clinical trial; Novel application of influenza vaccine; Transcutaneous vaccination(hair follicular targeting); Intradermal vaccination(micro-needle)