T-cell And General Immune Response to Seasonal Influenza Vaccine (SLVP018) Year 4, 2012

Protective Mechanisms Against a Pandemic Respiratory Virus: B-cell, T-cell, and General Immune Response to Seasonal Influenza Vaccine. Year 4, 2012

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

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: TIV; Biological: LAIV; Biological: High-Dose TIV

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Group B: 18-30 yo identical twins (LAIV); Participants to receive FluMist® LAIV by nasal spray.	Biological: LAIV; Live, attenuated influenza vaccine for Intranasal Spray; Other Names: FluMist®
Other: Group B: 18-30 yo identical twins (TIV); Participants to receive Fluzone® standard TIV	Biological: TIV; Influenza Virus Vaccine Suspension for Intramuscular Injection; Other Names: Fluzone® standard TIV
Other: Group D: 40-64 yo identical twins (TIV); Participants to receive Fluzone® standard TIV	Biological: TIV; Influenza Virus Vaccine Suspension for Intramuscular Injection; Other Names: Fluzone® standard TIV
Other: Group F: 65-100 yo identical twins (TIV); Participants to receive Fluzone® standard TIV	Biological: TIV; Influenza Virus Vaccine Suspension for Intramuscular Injection; Other Names: Fluzone® standard TIV
Other: Group F: 65-100 yo identical twins (High-Dose TIV); Participants to receive High-Dose Fluzone® standard TIV	Biological: High-Dose TIV; High-Dose Influenza Virus Vaccine supplied in a prefilled, single-dose syringe; Other Names: High-Dose Fluzone® TIV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Who Received Influenza Vaccine	Day 0

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Related Adverse Events	Day 0 to 28 post-immunization

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Principal Investigator: Mark Davis, PhD, Stanford University; Principal Investigator: Garry Nolan, PhD, Stanford University; Principal Investigator: Ann Arvin, MD, Stanford University

Publications and helpful links

General Publications

• Kay AW, Fukuyama J, Aziz N, Dekker CL, Mackey S, Swan GE, Davis MM, Holmes S, Blish CA. Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy. Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):14506-11. doi: 10.1073/pnas.1416569111. Epub 2014 Sep 22.
• Kay AW, Bayless NL, Fukuyama J, Aziz N, Dekker CL, Mackey S, Swan GE, Davis MM, Blish CA. Pregnancy Does Not Attenuate the Antibody or Plasmablast Response to Inactivated Influenza Vaccine. J Infect Dis. 2015 Sep 15;212(6):861-70. doi: 10.1093/infdis/jiv138. Epub 2015 Mar 4.
• O'Gorman WE, Huang H, Wei YL, Davis KL, Leipold MD, Bendall SC, Kidd BA, Dekker CL, Maecker HT, Chien YH, Davis MM. The Split Virus Influenza Vaccine rapidly activates immune cells through Fcgamma receptors. Vaccine. 2014 Oct 14;32(45):5989-97. doi: 10.1016/j.vaccine.2014.07.115. Epub 2014 Sep 6.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2012
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: January 12, 2017
• First Submitted That Met QC Criteria: January 12, 2017
• First Posted (Estimate): January 16, 2017

Study Record Updates

• Last Update Posted (Actual): May 22, 2017
• Last Update Submitted That Met QC Criteria: May 18, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Live, attenuated influenza vaccine; Inactivated influenza vaccine; Adult and elderly identical twins; Adult fraternal twins
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: SU-17219-2012; 2U19AI057229-06 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO