This is one project of a larger ongoing study related to the immune system's response to the flu virus. This study is designed to investigate the immune response to the live attenuated influenza vaccine (LAIV) vs. the Inactivated Influenza Vaccine (IIV) in identical and fraternal twins.

This is a Phase I mechanistic study of licensed influenza vaccines. The study requires 10 monozygotic and 10 dizygotic sets of twins (40 total participants) to enroll.

The duration of the study for an individual volunteer will be 4 weeks including screening and active participation. The study has a total of 3 visits.

First visit: Procedures during this visit are: Informed consent process, enrollment, study assessments, 20 ml blood draw, and vaccination. Participants will be randomized to receive either LAIV or IIV.

The time required to complete the first study visit will be about 30-40 minutes.

2nd (day 7 post vaccination) and 3rd (day 28 post vaccination ) visit: 20 ml blood will be obtained and the visit will take approximately 15 minutes.

Inclusion Criteria:

1. 2-20 year old male and female patients
2. Willing and able to complete the informed consent process
3. Availability of twin pair also agreeable and eligible for study inclusion
4. Availability for follow-up for the planned duration of the study
5. Acceptable medical history by review of inclusion/exclusion criteria

Exclusion Criteria:

1. Prior off-study vaccination with seasonal influenza vaccine within three months of study vaccination
2. Life-threatening reactions to previous influenza vaccinations
3. Asthma (contraindication for receipt of LAIV4)
4. Allergy to egg or egg products or to vaccine components including gentamicin, gelatin, arginine or MSG.
5. Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
6. History of immunodeficiency (including HIV infection)
7. Known or suspected impairment of immunologic function; may include significant liver disease, diabetes mellitus treated with insulin or moderate to severe renal disease
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 systemic glucocorticoids (corticosteroid nasal sprays and topical steroids are permissible). Use of oral steroids (<20mg prednisone-equivalent/day) may be acceptable after review by the investigator.
11. Participants in close contact with anyone who has a severely weakened immune system
12. 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).
13. 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.
14. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
15. Use of any anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet agents such as aspirin (except up to 325 mg. per day), Plavix, or Aggrenox will be reviewed by investigators to determine if study participation would affect the volunteer's safety or compliance with the protocol.
16. Has taken an influenza antiviral medication within 48 hours prior to study vaccination [If yes, may not eligible if unable to schedule at an appropriate interval].
17. Receipt of blood or blood products within the past 6 months or planned used during the study.
18. Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol
19. Receipt of an inactivated vaccine 14 days prior to study enrollment, or planned vaccinations prior to completion of last study visit (~ 14 days after study vaccination)
20. Receipt of a live, attenuated vaccine within 60 days prior to enrollment of planned vaccination prior to completion of last study visit (~ 14 days after study enrollment)
21. Need for allergy immunization (that cannot be postponed) until after the last study visit.
22. History of Guillain-Barre# syndrome
23. Pregnant woman
24. Breastfeeding woman
25. Use of investigational agents within 30 days prior to enrollment or planned use during the study.
26. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment or donation of platelets within 2 weeks of enrollment or planned donation prior to completion of the last visit.
27. 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.

1 year