Immunogenicity of Adjuvanted or Non-adjuvanted H5N1 Booster Vaccine in Adults Primed to A/VN/1194/04
Immunogenicity of Adjuvanted or Non-adjuvanted H5N1 Booster Vaccine in Adults Primed to A/VN/1194/04
This study focuses on pre-pandemic priming of man against H5 influenza with the goal of
 mounting a robust antibody response to small quantities of vaccine either before or during an
 H5 pandemic.
OBJECTIVES:

 Immunogenicity objectives

 1. To evaluate the magnitude of the antibody responses to one or two 'priming' 0.5mL
 intramuscular (IM) doses of an MF59-adjuvanted A/Vietnam/1194/2004 (H5N1 Clade 1)
 influenza vaccine, each dose containing 7.5μg of H5N1 haemagglutinin, in immunologically
 naïve subjects;

 2. To examine the kinetics of the antibody responses to one 0.5mL 'booster' intramuscular
 dose of antigenically drifted MF59-adjuvanted vaccine, or non-adjuvanted antigenically
 drifted vaccine, given at doses of 3.75 or 7.5μg, in subjects primed with one or two
 doses of an MF59-adjuvanted A/Vietnam/1194/2004 (H5N1 Clade 1) influenza vaccine;

 3. To evaluate the magnitude of the antibody responses to one 0.5mL 'booster' intramuscular
 dose of antigenically drifted MF59-adjuvanted vaccine, or non-adjuvanted antigenically
 drifted vaccine, given at doses of 3.75μg or 7.5μg, in subjects primed with one or two
 doses of an MF59-adjuvanted A/Vietnam/1194/2004 (H5N1 Clade 1) influenza vaccine;

 4. To evaluate the breadth of the antibody responses induced by 'priming' (see 1., above),
 and 'booster' vaccination regimens (see 2., and 3., above), with respect to a
 representative range of antigenically distinct H5N1 viruses (wild-type and attenuated);
 and

 5. To evaluate the persistence of the antibody responses induced by 'priming' (see 1.,
 above), and 'booster' vaccination regimens (see 2., and 3., above).

 Safety objective

 1. To evaluate the safety of the administration of one or two 'priming' 0.5mL intramuscular
 (IM) doses of an MF59-adjuvanted A/Vietnam/1194/2004 (H5N1 Clade 1) influenza vaccine (each
 dose containing 7.5μg of H5N1 haemagglutinin), in immunologically naïve subjects, followed by
 one 3.75μg or 7.5μg 'booster' dose of antigenically drifted MF59-adjuvanted H5N1 vaccine, or
 non-adjuvanted antigenically drifted H5N1 vaccine.
Inclusion Criteria:

 1. Subjects 18 to 59 years of age, or 60 years of age and older, mentally competent, who
 have signed an informed consent form after having received a detailed explanation of
 the study protocol;

 2. Are in good health or have one or more stable (See footnote) medical conditions, as
 determined by:

 1. Medical history,

 2. Physical examination,

 3. Clinical judgment of the medical investigator;

 3. Are able to understand and comply with all study procedures and to complete study
 diaries, can be contacted, and will be available for study visits.

 4. Subjects who experienced fever (defined as axillary temperature >38oC) within 3 days
 prior to Visit 1;

 5. Subjects who are pregnant or breastfeeding;

 6. Females of childbearing potential who refuse to use an acceptable method of birth
 control for a period of 56 days before and after each vaccination. Adequate
 contraception is defined as hormonal (e.g., oral, injection, transdermal patch,
 implant, cervical ring), barrier (e.g., condom with spermicide or diaphragm with
 spermicide), intrauterine device (e.g., IUD), monogamous relationship with
 vasectomised partner who has been vasectomised for 6 months or more prior to the
 subject's study entry, or abstain from heterosexual intercourse (e.g., through sexual
 orientation or religious or other beliefs about premarital intercourse);

 7. Subjects with any serious disease, including:

 1. cancer,

 2. acute or progressive hepatic disease,

 3. acute or progressive renal disease,

 4. chronic pulmonary disease requiring home oxygen therapy,

 5. active neurological disorder,

 6. autoimmune disease (including rheumatoid arthritis);

 8. Subjects for whom surgery is planned during the study period;

 9. Subjects with a bleeding diathesis;

 10. Subjects with hypersensitivity to eggs, chicken protein, chicken feathers, influenza
 viral protein, neomycin or kanamycin, or any other component of the study vaccine;

 11. Subjects with a history of any neurological symptoms and signs, or anaphylactic shock
 following administration of any vaccine;

 12. Subjects with known or suspected impairment/alteration of immune function, for
 example, resulting from:

 1. receipt of oral immunosuppressive therapy (e.g., corticosteroid therapy or cancer
 chemotherapy) (long-term, inhaled steroids for asthma management is acceptable),

 2. receipt of immunostimulants or interferon,

 3. receipt of parenteral immunoglobulin preparation, blood products, and/or plasma
 derivatives within 3 months prior to Visits 1 (Day 1), 2 (Day 22), or 5 (Day
 382), or planned during the full length of the study,

 4. high risk from developing an immunocompromising disease;

 13. Actual or planned receipt of another vaccine during the period 3 weeks before to 3
 weeks after vaccination on Days 1, 22, and 382;

 14. Subjects with a history of (or current) drug or alcohol abuse (20g/day for females;
 30g/day for males) that in the investigator's opinion would interfere with safety of
 the subject or the evaluation of the study objectives;

 15. Subjects who are unable to lead an independent life either physically or mentally;

 16. Have participated in a previous study of H5 avian influenza vaccine;

 17. Have been previously vaccinated with a vaccine containing MF59 or similar adjuvant;

 18. Subjects with any condition, which, in the opinion of the Investigator, might
 interfere with the evaluation of the study objectives.

 Exclusion Criteria: