This study will investigate markers, mechanisms and define general predictors for immunological health by comparing influenza vaccine responses in monozygotic and dizygotic twins.

The investigators plan to study the response to different influenza vaccines much more broadly and deeply across different age groups and with different vaccine modalities and to probe the influence of genetics on these responses using monozygotic and dizygotic twins. On an investigational basis, the investigators plan to compare various immunological responses, identify age-specific biomarkers or clusters of markers, quantify the frequency of influenza-specific T-cells pre- and post-vaccination, and determine the effective breadth of T-cell repertoire to an influenza vaccine within an individual as a function of age and to what degree this is genetically determined.

Twin group B will will be randomly assigned to receive a single dose of inactivated vaccine, either the trivalent inactivated influenza vaccine (TIV) or intranasal live, attenuated influenza vaccine (LAIV). Twin Groups C-E will receive a single administration of TIV. Group F, elderly participants, will be randomly assigned to receive a single dose of inactivated vaccine, either the standard dose or the high-dose TIV. Blood samples to conduct the assays described will be taken at pre-immunization, Days 7-10 and 28 post-immunization.

Groups A, C and E were not enrolled for this year of the five year annual study.

Inclusion Criteria:

1. Otherwise healthy, ambulatory adults, ages 18-30 years (identical or fraternal twin pairs), 40-64 years (identical or fraternal twin pairs) or 65-100 years (identical twin pairs).
2. Willing to complete the informed consent process.
3. Availability for follow-up for the planned duration of the study at least 28 days after immunization.
4. Acceptable medical history and vital signs.

Exclusion Criteria:

1. Prior off-study vaccination with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV) in Fall 2012
2. Allergy to egg or egg products, or to vaccine components (including gentamicin, gelatin, arginine or MSG (LAIV for Group B only), and thimerosal (if TIV multidose vials used)
3. Life-threatening reactions to previous influenza vaccinations
4. Active systemic or serious concurrent illness, including febrile illness the day of vaccination
5. History of immunodeficiency (including HIV infection)
6. Known or suspected impairment of immunologic function, including, but not limited to, clinically significant liver disease, diabetes mellitus treated with insulin, moderate to severe renal disease or any other chronic disorder which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.
7. Blood pressure >150 systolic or > 95 diastolic at Visit 1
8. Hospitalization in the past year for congestive heart failure or emphysema.
9. Chronic Hepatitis B or C
10. Recent or current use of immunosuppressive medication, including glucocorticoids (corticosteroid nasal sprays, topical steroids and inhaled steroids are permissible). Use of oral steroids (<20mg prednisone-equivalent/day) may be acceptable after review by the investigator.
11. Malignancy, other than squamous cell or basal cell skin cancer (includes solid tumors such as breast cancer or prostate cancer with recurrence in the past year, and any hematologic cancer such as leukemia).
12. 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.
13. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
14. Use of any anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet agents such as aspirin (except aspirin up to 325 mg.day), Plavix, or Aggrenox must be reviewed by investigator to determine if this would affect the volunteer's safety.
15. Receipt of blood or blood products within the past 6 months or planned receipt of blood products prior to completion of study visits.
16. Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol
17. Receipt of inactivated vaccine 14 days prior to study vaccination, or planned non-study vaccination prior to completion of Visit 03 (~Day 28 after the study vaccination)
18. Receipt of live, attenuated vaccine within 60 days of vaccination, or planned non-study vaccination prior to completion of Visit 03 (~Day 28 after the study vaccination)
19. Need for allergy immunization (that cannot be postponed) during the study period V01 to V03 (~Day 28)
20. History of Guillain-Barre Syndrome
21. Pregnant or lactating woman
22. Use of investigational agents within 30 days prior to enrollment or planned use of investigational agents prior to completion of study visits.
23. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment or planned blood donation prior to completion of Visit 03 ( ~28 Day after study vaccination)
24. A current member of the clinical study team.
25. 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.
26. Asthma or history of wheezing (for Group B volunteers only)
27. Participants in close contact with anyone who has a severely weakened immune system should not receive LAIV (for Group B volunteers only)

Day 0 to 28 of study participation

Clinical assessment performed at each visit