Heterosubtypic Immune Responses to Influenza in Older People

STUDY OBJECTIVES:

Immunological objectives

• To evaluate heterosubtypic neutralising antibody to influenza viruses in older people
• To evaluate heterosubtypic neutralising antibody responses to human and non-human influenza viruses following seasonal influenza vaccine
• To evaluate homologous and heterosubtypic neutralising antibody responses to human and non-human influenza viruses after MF59-adjuvanted H5N1 vaccine;
• To evaluate cellular B and T cell responses to influenza H5 in non-exposed subjects who exhibit anti-H5 neutralising antibodies before and after seasonal (TIV) or pandemic H5 vaccination
• To identify epitopes on the influenza haemagglutinin to which anti-H5 neutralising antibodies in sera from non-exposed subjects are directed Safety Objectives
• To evaluate safety of one or two IM doses of MF59-adjuvanted A/Vietnam/1194/2004 (H5N1) influenza vaccine, containing 7.5 μg of H5 antigen in adult subjects
• To evaluate safety of one IM dose of seasonal influenza vaccine, containing 15 μg of H1, H3 and B antigen in adult subjects

Hypotheses:

• Heterosubtypic cross reacting antibodies to influenza exist in some elderly subjects and can be boosted by a single dose of (a) seasonal TIV or (b) pandemic influenza vaccination
• Heterosubtypic cross reacting antibodies to influenza do not exist in younger subjects and cannot be induced by (a) seasonal TIV or (b) pandemic influenza vaccination

Inclusion criteria

• Subjects aged over 18 years of age, mentally competent, who have signed an informed consent form after having received a detailed explanation of the study protocol;
• Subjects willing to be enrolled in the vaccine study if appropriate from prescreening blood test results
• In good health as determined by:

• medical history,
• physical examination,
• clinical judgment of the Investigator;
• Able to understand and comply with all study procedures and to complete study diaries, can be contacted, and will be available for study visits

Exclusion criteria

• Receipt of another investigational agent within 4 weeks, or before completion of the safety follow-up period in another study, whichever is longer, prior to enrollment and unwilling to refuse participation in another clinical study through the end of the study;
• Subjects who experienced any acute disease or infection requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable) within the past 7 days before Visit 1 or any visit where trial vaccination is planned;
• Subjects who experienced fever (within 3 days prior to Visit 1;
• Subjects who are pregnant or breastfeeding;
• Females of childbearing potential who refuse to use an acceptable method of birth control for the duration of the study.
• Subjects with any serious disease, such as:

• cancer,
• autoimmune disease (including rheumatoid arthritis),
• progressive chronic pulmonary disease (stable controlled respiratory disease including asthma is allowed),
• acute or progressive hepatic disease,
• acute or progressive renal disease;
• Subjects for whom elective surgery is planned during the study period;
• Subjects with bleeding diathesis;
• Subjects with hypersensitivity to eggs, chicken protein, chicken feathers, influenza viral protein, neomycin or polymyxin or any other component of the study vaccine;
• Subjects with a history of any neurological symptoms or signs, or anaphylactic shock following administration of any vaccine;
• Subjects with known or suspected impairment/alteration of immune function, for example, resulting from:

• receipt of immunosuppressive therapy (any corticosteroid therapy or cancer chemotherapy),
• receipt of immunostimulants,
• receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to Visit 1 or planned during the full length of the study,
• high risk for developing an immunocompromising disease;
• Receipt of another vaccine within 3 weeks prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination;
• Subjects with a history of (or current) drug or alcohol abuse that in the investigator's opinion would interfere with safety of the subject or the evaluation of study objectives;
• Subjects with any condition, which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.

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