In this study the investigators are trying to understand how immune function declines in the elderly using annual influenza vaccinations as a model system. The longitudinal study began in 2007 and continued through early 2017.

Participants ranging in age from 18 to 100 at time of initial enrollment will be immunized annually with the seasonal influenza vaccine, Fluzone, on Day 0. Follow-up visits will be conducted on Day 6-8 and Day 28. Unsolicited adverse events are collected from immunization until the Day 28 visit, serious adverse events are collected for the entire time of study participation. A blood sample is collected pre-immunization and at each follow-up visit. Volunteers will be followed for up to 11 years, those too frail to come in for visits received annual phone calls to monitor health. Last annual influenza vaccines were given in Fall 2015.

The main basic research effort will be to collect safety data and follow medical history events in elderly and younger control subjects. Investigators will also look at immune responses to influenza vaccination. In 2008, 2012 and 2014, the cohort added additional participants to replace those who had withdrawn.

Beginning in 2014, those participants 65 years and older were immunized with High Dose trivalent Fluzone and younger participants received the quadrivalent formulation of Fluzone.

Inclusion Criteria:

• Age 18-30, 60-79, or 80-100 years, inclusive at time of initial enrollment
• General good health and ambulatory at time of enrollment
• No acute illness at time of vaccination
• Willing and able to sign Informed Consent
• Available for follow-up for the planned duration of the study
• Acceptable medical history by screening evaluation and brief clinical assessment
• All female subjects of childbearing potential must use an acceptable method of contraception and not become pregnant for the duration of the clinical phase of the study (approximately 1 month to completion of Visit 3). (Acceptable contraception may include implants, injectables, combined oral contraceptives, effective intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner).

Exclusion Criteria:

• Prior off-study vaccination with trivalent or quadrivalent (depending no year) influenza vaccine (TIV or IIV4) or live attenuated influenza vaccine (LAIV) in the current flu season
• Allergy to egg or egg products
• Allergy to vaccine components, including thimerosal
• Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
• History of immunodeficiency
• Any chronic disorder which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.
• Blood pressure >150 systolic or > 95 diastolic at Visit 1
• Chronic Hepatitis B or C.
• Recent or current use of systemic immunosuppressive medication, including glucocorticoids (corticosteroid nasal sprays and inhaled steroids are permissible). Use of oral steroids (<20mg prednisone-equivalent/day) may be acceptable after review by the investigator.
• Autoimmune disease (including rheumatoid arthritis treated with immunosuppressive medication such as Plaquenil, methotrexate, prednisone, Enbrel) which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.
• History of blood dyscrasias or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
• Use of anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet agents such as aspirin, Plavix, Aggrenox must be reviewed by investigator to determine if this would affect the volunteer's safety.
• Receipt of blood or blood products within the past 6 months
• Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol
• Receipt of inactivated vaccine within 14 days prior to vaccination
• Receipt of live, attenuated vaccine within 60 days of vaccination
• History of Guillain-Barré Syndrome
• Pregnant or lactating woman
• Use of investigational agents within 30 days prior to enrollment
• Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment
• Any condition which, in the opinion of the investigator, might interfere with volunteer safety, study objectives or the ability of the participant to understand or comply with the study protocol.

The NIH Human Immunology Project Consortium (HIPC) data repositories (ImmPORT) may store the results of the research assays results. Genetic data that is developed in this study may be made available to other researchers through the National Center for Biotechnology Information (NCBI) databases. Results from research assays will be labeled with a unique ID code and the volunteer identity (except for age) will not be disclosed.