Routes of Immunization and Flu Immune Responses (FLUWAY)
Biological: INTANZA® 15
Biological: INTANZA® 15 T
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
|Official Title:||Impact of Immunization Routes on the Immune Response to Influenza Vaccine|
- CD8 T cell responses [ Time Frame: 21 days ] [ Designated as safety issue: No ]CD8 T cell responses against the specific vaccine strain will be measured at baseline and day 21 after vaccination by flow cytometry. Secretion of cytokines measured by intracellular staining will be compared between TC, ID and IM routes of vaccination.
- Safety [ Time Frame: 5 months ] [ Designated as safety issue: Yes ]Safety will be assessed at each visit by recording clinical local and systemic tolerance including reporting of adverse events. Frequency and severity of local and systemic adverse events following vaccination will be compared between TC, ID and IM vaccination groups.
- Haemagglutination Inhibition [ Time Frame: 5 months ] [ Designated as safety issue: No ]Haemagglutination Inhibition and microneutralization assays will be performed at day0, day 21 and month 5 after vaccination to define the humoral response against a vaccine-homologous virus that meets or exceeds the EMEA (CHMP) guidance targets for influenza vaccine seroconversion rate (SCR), seroprotection rate (SPR), and geometric mean fold rise (GMFR).
- CD4 T cell responses [ Time Frame: 21 days ] [ Designated as safety issue: No ]CD4 T cell responses against the specific vaccine strain will be measured at baseline and day 21 by intracellular staining and flow cytometry. Effector CD4 T cell responses will be compared between TC, ID and IM vaccination groups.
- Memory CD8 and CD4 T cell responses [ Time Frame: 5 months ] [ Designated as safety issue: No ]Memory CD8 and CD4 T cell responses against the specific vaccine strain will be assessed by flow cytometry 5 month after vaccination by TC, ID and IM routes.
- Inflammation [ Time Frame: 1 day ] [ Designated as safety issue: No ]Inflammation and systemic innate immune response will be assessed on day 1 after vaccination (compared with the basal inflammatory status) by studying the transcriptional profile of blood cells (microarrays) and inflammatory cytokines dosage in the serum.
|Study Start Date:||October 2012|
|Study Completion Date:||April 2013|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
Experimental: Arm A
Type Vaccine Name: INTANZA® 15 T Description : transcutaneous vaccination
Biological: INTANZA® 15 T
Active Comparator: Arm B
Type: Vaccine Name: INTANZA® 15ug Description : intradermal vaccination
Biological: INTANZA® 15
Active Comparator: Arm C
Type : Vaccine Name: Vaxigrip® Description :Intramuscular vaccination
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01707602
|GH Cochin - Broca - Hôtel-Dieu CIC BT505|
|PARIS Cedex 14, France, 75679|
|Principal Investigator:||Odile LAUNAY, M.D. Ph. D||Assistance Publique - Hôpitaux de Paris|