Safety and Immunogenicity of a Cell Culture-derived Influenza Vaccine in Healthy Adults and Elderly

• To evaluate safety and tolerability of a single IM injection of the cell culture-derived and egg-derived influenza subunit vaccines.
• To evaluate immunogenicity of a single IM injection of the cell culture-derived and egg-derived influenza subunit vaccines, in compliance with the criteria outlined in the EMEA recommendations (CPMP/BWP/2490/00, CPMP/BWP/214/96)

• Safety and tolerability of a single 0.5 mL IM injection (in the deltoid muscle of the non-dominant arm) of the cell culture-derived and egg-derived influenza subunit vaccines. [ Time Frame: 6 months post vaccination ] [ Designated as safety issue: Yes ]
• Non-inferiority of the cell culture-derived vaccines as compared to a conventional egg-derived vaccine by comparing the correlates of protection (seroprotection, seroconversion and sufficient increase in GMT) after a single IM injection. [ Time Frame: 21 days post vaccination ] [ Designated as safety issue: No ]
  Noninferiority of the correlates of protection (seroprotection, seroconversion and sufficient increase in GMT) of a single 0.5 mL IM injection (in the deltoid muscle of the non-dominant arm) of the cell culture-derived influenza subunit vaccine versus a single 0.5 mL IM injection (in the deltoid muscle of the non-dominant arm) of the egg-derived influenza subunit vaccine.

The present study aims to evaluate the safety and immunogenicity of the new influenza subunit vaccine produced in Madin Darby Canine Kidney (MDCK) cells in healthy adult and elderly subjects.

• Biological: cell-derived trivalent subunit influenza vaccine
  1 dose 0.5 ml cell-derived influenza vaccine, administered in the deltoid muscle
• Biological: egg-derived trivalent subunit influenza vaccine
  1 dose 0.5ml egg-derived influenza virus vaccine, administered in the deltoid muscle

• Experimental: Arm 1: Cell culture-derived influenza vaccine
  Intervention: Biological: cell-derived trivalent subunit influenza vaccine
• Active Comparator: Arm 2: Egg-derived influenza virus vaccine
  Intervention: Biological: egg-derived trivalent subunit influenza vaccine

Inclusion Criteria:

1. 18 to 60 years of age (first age group) OR over 60 years of age (second age group)
2. mentally competent to understand the nature, the scope and the consequences of the study
3. able and willing to give written informed consent prior to study entry
4. available for all the visits scheduled in the study
5. residence in the study area

6. in good health as determined by:

   1. medical history,
   2. physical examination,
   3. clinical judgment of the investigator.

Exclusion Criteria:

1. unable or unwilling to give written informed consent to participate in the study
2. suffering from an acute infectious disease

3. any serious disease such as:

   1. cancer (except for benign or localized skin cancer and non metastatic prostate cancer not currently treated with chemotherapy),_
   2. autoimmune disease (including rheumatoid arthritis),
   3. advanced arteriosclerotic disease or complicated diabetes mellitus,
   4. chronic obstructive pulmonary disease (COPD) requiring oxygen therapy,
   5. acute or progressive hepatic disease,
   6. acute or progressive renal disease,
   7. congestive heart failure
4. surgery planned during the study period
5. bleeding diathesis
6. history of hypersensitivity to any component of the study medication or chemically related substances, such as allergy to eggs or egg products

7. known or suspected impairment/alteration of immune function resulting from:

   1. receipt of immunosuppressive therapy (any cortical steroid or cancer chemotherapy),
   2. receipt of immunostimulants,
   3. receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within the past 3 months and for the full length of the study,
   4. high risk for developing an immunocompromising disease within the past 6 months
8. history of drug or alcohol abuse
9. laboratory confirmed influenza disease in the past 6 months
10. received influenza vaccine within the past 6 months
11. received another vaccine or any investigational agent within the past 60 days, or plans vaccination within 3 weeks following the study vaccination
12. any acute respiratory disease or infections requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable) or experienced fever _ 38°C within the past 3 days
13. pregnant women or women who refuse to use a reliable contraceptive method throughout the study (180 days)
14. any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.