Evaluation of Metabolic Predictors of Influenza Vaccine Immune Response in the Singapore Elderly Population - the DYNAMIC Trial

Inclusion Criteria:

• Age 65 and above at time of enrollment (up to age 100) and able to give informedconsent

• Determined by medical history, physical examination, and clinical judgment to begenerally healthy, with no immunosuppressive conditions and having stable currentmedical conditions. Subjects with preexisting, stable disease, defined as notrequiring significant change in therapy or hospitalization for worsening of disease 12weeks prior to receipt of study vaccine are eligible. A change in dose or therapywithin a treatment category (e.g., change from one non-steroidal anti-inflammatorydrug to another) is allowed. A change to a new therapy category (e.g., surgery oraddition of a new pharmacological class) is only allowed if it is not caused byworsening disease.

• Is eligible for seasonal influenza vaccine

• Is available for all planned study visits

• Is willing to follow study procedures

• Able to follow study procedures (questionnaires, blood draws, vaccination) in theopinion of the investigator

Exclusion Criteria:

• A change to a new therapy category caused by worsening disease is consideredsignificant and will disqualify subject from participating in the study

• Subjects reporting any symptoms suggestive of influenza, influenza-like illness, orrespiratory illness

• Vaccination with any licensed or experimental influenza vaccine within the past 10months

• Intent to receive any other investigational vaccine or agent during the course of thestudy

• Intent to receive other licensed vaccines during the course of the study (does notapply for pandemic or post-exposure prophylaxis scenario

• History of severe adverse reaction associated with an influenza vaccine

• Allergic to egg proteins (egg or egg products) and chicken proteins

• Known or suspected immunodeficiency or receiving treatment with immunosuppressivetherapy including cytotoxic agents in past 6 months e.g., transplant recipients onactive immunosuppression, patients with cancer, HIV, or autoimmune disease.

• Long-term systemic corticosteroid therapy (prednisolone ≥ 7.5mg/day or equivalent formore than 2 consecutive weeks within the past 3 months) Note: If systemiccorticosteroids have been administered short term for treatment of an acute illness,subjects will be excluded from the study until corticosteroid therapy had beendiscontinued for at least 30 days.

• History of Guillain-Barré syndrome

• Serious chronic medical condition including: metastatic malignancy, severe chronicobstructive pulmonary disease requiring supplemental oxygen, CKD stage 3 and above,end stage renal disease with or without dialysis, clinically unstable cardiac disease,or any other disorder that in the investigator's opinion should preclude the subjectfrom participating in the study

• Bariatric surgery, GI malabsorption disorders

• Recurrent Falls (≥2 falls in the past 12 months)

• Osteoporosis with or without pathological fractures

• Current or recently completed high dose vitamin D supplementation within the past 3months (defined as daily cholecalciferol dose of 2000 IU or higher, weekly 50,000 IUor intramuscular calcitriol)

• Receipt of any blood products, including immunoglobulin, within six months of studyenrollment

• Donated blood within last 58 days

• Current anticoagulant therapy or a history of bleeding diathesis (includingthrombocytopenia with platelet count < 50,000) that would contraindicate intramuscular (IM) injection (Note: antiplatelet drugs such as aspirin and clopidogrel arepermitted)

• Moderate or severe acute illness/infection (according to investigator judgement) onthe day of vaccination, or febrile illness (temperature ≥ 37.5°C). A prospectivesubject should not be included in the study until the condition has resolved or thefebrile event has subsided.

• Any medical condition that would, in the opinion of the investigator, interfere withthe evaluation of the study objectives