T-cell And General Immune Response to Seasonal Influenza Vaccine (SLVP018) Year 2, 2010

Phase 4

Completed

• Conditions: Influenza
• Interventions: Biological: Fluzone® (intramuscular); Biological: High Dose Fluzone® (intramuscular)

• Registration Number: NCT03022396
• Lead Sponsor: Stanford University

Brief Summary

This study will investigate response to influenza vaccines in monozygotic and dizygotic twins of different ages.

Detailed Description

The investigators plan to study the response to influenza vaccines much more broadly and deeply across different age groups and with different vaccine formulations and to probe the influence of genetics on these responses using monozygotic and dizygotic twins. On an investigational basis, 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 Groups A-E will receive a single administration of the 2010-2011 formulation of seasonal trivalent inactivated influenza vaccine (TIV). Group F, elderly monozygotic twin participants, will be randomly assigned to receive a single dose of inactivated vaccine, either the usual 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. Each twin is counted as a single participant. All reporting numbers reflect the number of participants, not the number of twin pairs.

Study Timeline

• Study Start: 2010-09
• Primary Completion: 2011-01
• Study Completion: 2011-01
• Study First Submitted: 2017-01-12
• Study First Submitted QC: 2017-01-13
• Study First Posted: 2017-01-16
• Results First Submitted: 2017-01-17
• Status Verified: 2017-08
• Results First Submitted QC: 2017-08-15
• Last Update Submitted: 2017-08-15
• Results First Posted: 2017-08-21
• Last Update Posted: 2017-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 82

Inclusion Criteria

1. Otherwise healthy, ambulatory children or adults, ages 8-17 years (identical twins), 18-30 years (identical or fraternal twins), 40-59 years (identical or fraternal twins) or 70-100 years (identical twins).
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.
5. All female of childbearing potential, must use an acceptable method of contraception and not become pregnant for the duration of the study (approximately 1 month or to completion of Visit 3). (Acceptable contraception includes implants, injectables, combined oral contraceptives, effective intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner).

Exclusion Criteria

1. Prior off-study vaccination with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV) in Fall 2010
2. Allergy to egg or egg products, or to vaccine components, including thimerosal (if TIV multidose vials used)
3. Life-threatening reactions to previous influenza vaccinations
4. Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
5. History of immunodeficiency
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 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, Plavix, 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
16. Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol
17. Inactivated vaccine 14 days prior to vaccination
18. Live, attenuated vaccine within 60 days of vaccination
19. History of Guillain-Barre Syndrome
20. Pregnant or lactating woman
21. Use of investigational agents within 30 days prior to enrollment
22. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment
23. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A: age 8-17 yo identical twins	Fluzone® (intramuscular)	Individual twins to receive Fluzone® (intramuscular)
Group B: age 18-30 yo identical twins	Fluzone® (intramuscular)	Individual twins to receive Fluzone® (intramuscular)
Group C: age 18-30 yo fraternal twins	Fluzone® (intramuscular)	Individual twins to receive Fluzone® (intramuscular)
Group E: age 40 - 59 yo fraternal twins	Fluzone® (intramuscular)	Individual twins to receive Fluzone® (intramuscular)
Group F: age 70 - 100 yo identical twins	High Dose Fluzone® (intramuscular)	Individual twins to receive Fluzone® (intramuscular) or High Dose Fluzone® (intramuscular)
Group F: age 70 - 100 yo identical twins	Fluzone® (intramuscular)	Individual twins to receive Fluzone® (intramuscular) or High Dose Fluzone® (intramuscular)
Group D: age 40 - 59 yo identical twins	Fluzone® (intramuscular)	Individual twins to receive Fluzone® (intramuscular)

Primary Outcome Measures

Name	Time	Method
Number of Individual Twins Who Received Influenza Vaccine	Day 0 to 28	All numbers reported are the number of participants, not the number of twin pairs. Each member of a twin was counted individually as a participant.

Secondary Outcome Measures

Name	Time	Method
Number of Individual Twins With Related Adverse Events	Day 0 to 28 post-immunization