Adaptive Immune Responses and Repertoire in Influenza Vaccination and Infection (SLVP031)

Inclusion Criteria:

1. Otherwise healthy 18-49 years old identical (MZ) twins identified as DR1501+ or DR0701+ by lab assay results. Both twins in the pair must be willing to participate in the study.
2. Willing to complete the informed consent process
3. Availability for follow-up for the planned duration of the study
4. Acceptable medical history by review of inclusion/exclusion criteria and vital signs.

Exclusion Criteria:

1. Prior off-study vaccination with the current year's seasonal influenza vaccine.
2. Allergy to egg or egg products or to vaccine components including gentamicin, gelatin, arginine or MSG
3. Life-threatening reactions to previous influenza vaccinations
4. Asthma (a contraindication for receipt of LAIV4)
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, 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.
8. Blood pressure \>150 systolic or \>95 diastolic at first study visit and the day of vaccination.
9. Hospitalization in the past year for congestive heart failure or emphysema.
10. Chronic Hepatitis B or C.
11. Recent or current use of immunosuppressive medication, including systemic glucocorticoids (corticosteroid nasal sprays and topical steroids are permissible in all groups; inhaled steroid use is not permissible)
12. Participants who care for severely immunosuppressed persons that require a protective environment should not receive LAIV, or should avoid contact with such persons for 7 days after receipt, given the theoretical risk for transmission of the live attenuated vaccine virus to close contacts. \[If yes, may be ineligible\]
13. 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).
14. 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.
15. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
16. 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 must be reviewed by investigator to determine if this would affect the volunteer's safety.
17. Has taken an influenza antiviral medication within 48 hours prior to study vaccination \[If yes, may not eligible if unable to schedule at an appropriate interval\].
18. Receipt of blood or blood products within the past 6 months or planned used during the study.
19. Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol
20. Receipt of an inactivated vaccine 14 days prior to study enrollment, or planned vaccinations prior to completion of last study visit ( \~ 28 days after study vaccination)
21. Receipt of a live, attenuated vaccine within 60 days prior to enrollment of planned vaccination prior to completion of last study visit (\~ 28 days after study vaccination)
22. Need for allergy immunization (that cannot be postponed) during the study period.
23. History of Guillain-Barré syndrome
24. Pregnant or lactating 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 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.