Immunogenicity and Safety of the Seasonal Flu Vaccine in Elderly and in SOT Recipients

Study Overview
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Brief Summary
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This study will assess the effect of a different dose of the seasonal flu vaccine 2013-2015 on the immune response to improve the investigators understanding of cellular and humoral immune responses induced. The scope of this study is to determine the profile of cellular activation and antibody production in the ageing immune system following flu immunization. This study will enroll 100 male or female subjects ≥65 year old and 90 transplant recipients. These persons will be deemed to be  at risk  in case of influenza infection and should be vaccinated according to Swiss Federal Office of Public Health. A medical doctor from the CHUV will inform the patients about the present study and ask them whether they would be willing to participate in the study. All subjects will be distributed between the two groups according to a computer-generated randomization sequence. The randomization will be done in blocks to ensure balance across groups. The participants and site staff will not be blinded due to the different administration assignments. Group 1 subjects will receive a single dose and group 2 subjects a double dose of MUTAGRIP® manufactured by Sanofi Pasteur containing A/California/7/2009 (H1N1); A/Texas/50/2012 (H3N2); B/Massachusetts/2/2012. Vaccine immunogenicity and safety will be assessed 1, 2, 4 and 24 weeks after vaccination. Study duration per volunteer is 6 months after vaccination.

Official Title
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Immunogenicity (Humoral and Cellular Immune Responses) and Safety of the Seasonal Flu Vaccine in Elderly and in SOT Recipients

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Single dose MUTAGRIP® influenza vaccine
* Drug: Double dose of MUTAGRIP® influenza vaccine


Participation Criteria
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Eligibility Criteria
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Elderly: Inclusion Criteria: Age ≥65 year old. Able to give informed consent. Necessity to receive influenza seasonal vaccination in 2013-2015. Availability for the duration of the study and willingness to attend all scheduled visits. Hemoglobin value ≥100 g/l , Leukocytes ≥3.5 G/L, Platelets count ≥100 G/l at the time of screening, or determined within 8 weeks before screening in the course of regular medical examination and validated by the medical doctor. Solid-organ transplant recipients Inclusion criteria Age ≥18 year old Solid organ transplantation >3 months before vaccination Stable patient followed at the outpatient clinic of the Transplantation Center Able to give informed consent. Necessity to receive influenza seasonal vaccination. Availability for the duration of the study and willingness to attend all scheduled visits. Exclusion criteria Previous life-threatening reaction to influenza vaccine (i.e. Guillain-Barre Syndrome) Ongoing therapy for rejection Febrile illness in the past two weeks Exclusion Criteria: Contraindication against seasonal flu vaccination. Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of the study vaccine, or planned use during the study period and safety follow-up. Immunodeficiency or chronic administration (defined as more than 14 consecutive days) of immunosuppressive or other immune-modifying drugs within six months prior to the first vaccine dose. (For corticosteroids, this will mean prednisone, or equivalent, ≥0.5 mg/kg/day. Inhaled and topical steroids are allowed). Hypersensitivity to the active substances, to any of the excipients, to eggs, chicken proteins, neomycin, formaldehyde and octoxinol 9. Acute disease at the time of enrollment [Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., temperature <38°C]. An unstable chronic condition (unstable chronic renal failure, unstable diabetes, unstable chronic cardiac condition, uncontrolled asthma, etc.). Receipt of blood-derived products (immunoglobulin; plasma) within 120 days prior to enrollment.

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1<br>Single dose of MUTAGRIP® containing A/California/7/2009 (H1N1); A/Texas/50/2012 (H3N2); B/Massachusetts/2/2012. | Drug: Single dose MUTAGRIP® influenza vaccine<br>* All subjects will receive either a single or double doses of MUTAGRIP® containing A/California/7/2009 (H1N1); A/Texas/50/2012 (H3N2); B/Massachusetts/2/2012. The double dose regimen will be administered at the same time.<br>|
| Experimental: Group 2<br>Double dose of MUTAGRIP® (one dose into the right deltoid area and the other one into the left deltoid area) containing A/California/7/2009 (H1N1); A/Texas/50/2012 (H3N2); B/Massachusetts/2/2012. | Drug: Double dose of MUTAGRIP® influenza vaccine<br>* All subjects will receive either a single or double doses of MUTAGRIP® containing A/California/7/2009 (H1N1); A/Texas/50/2012 (H3N2); B/Massachusetts/2/2012. The double dose regimen will be administered at the same time.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Immunogenicity | Humoral immune responses (antibodies directed against all three strains A/California/7/2009 (H1N1); A/Texas/50/2012 (H3N2); B/Massachusetts/2/2012). | weeks 2, 4 and 24 after vaccination | 
| Change from Baseline in Immunogenicity | Cellular immune responses directed against all three strains A/California/7/2009 (H1N1); A/Texas/50/2012 (H3N2); B/Massachusetts/2/2012. | weeks 1, 2, 4 and 24 after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events as a Measure of Safety and Tolerability | To evaluate safety and tolerability of the influenza vaccine (split virion, inactivated), MUTAGRIP®, administered in single or double dose. | 24 weeks after vaccination |