T-cell And General Immune Response to Seasonal Influenza Vaccine (SLVP018) - Year 1, 2009

• ClinicalTrials.gov Identifier: NCT01987349
• Recruitment Status: Completed
• First Posted: November 19, 2013
• Results First Posted: May 12, 2017
• Last Update Posted: May 12, 2017
• Sponsor: Stanford University
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): Cornelia L. Dekker, Stanford University

Study Description

Brief Summary:

This study will compare influenza vaccine responses in monozygotic and dizygotic twins.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: Fluzone® (intramuscular); Biological: FluMist® (intranasal)	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 72 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Protective Mechanisms Against a Pandemic Respiratory Virus: B- Cell, T-cell, and General Immune Response to Seasonal Influenza Vaccine. Year 1, 2009
• Study Start Date: September 2009
• Actual Primary Completion Date: January 2010
• Actual Study Completion Date: January 2010

Arms and Interventions

Arm	Intervention/treatment
Group A: age 8-17 yo identical twins; Participants will be randomized to receive either Fluzone® (intramuscular) or FluMist® (intranasal)	Biological: Fluzone® (intramuscular); Licensed seasonal trivalent inactivated influenza vaccine (IIV3); Biological: FluMist® (intranasal); Licensed trivalent seasonal live attenuated influenza vaccine (LAIV3)
Group B: 18-30 yo identical twins; Participants to receive FluMist® (intranasal)	Biological: FluMist® (intranasal); Licensed trivalent seasonal live attenuated influenza vaccine (LAIV3)
Group C: 18-30 yo fraternal twins; Participants to receive FluMist® (intranasal)	Biological: FluMist® (intranasal); Licensed trivalent seasonal live attenuated influenza vaccine (LAIV3)
Group D: 40-49 yo identical twins; Participants to receive FluMist® (intranasal)	Biological: FluMist® (intranasal); Licensed trivalent seasonal live attenuated influenza vaccine (LAIV3)
Group E: 40-49 yo fraternal twins; Participants to receive FluMist® (intranasal)	Biological: FluMist® (intranasal); Licensed trivalent seasonal live attenuated influenza vaccine (LAIV3)
Group F: 70-100 yo twins; Participants to receive Fluzone® (intramuscular)	Biological: Fluzone® (intramuscular); Licensed seasonal trivalent inactivated influenza vaccine (IIV3)
Group G: 70-100 yo non-twins; Participants to receive Fluzone® (intramuscular)	Biological: Fluzone® (intramuscular); Licensed seasonal trivalent inactivated influenza vaccine (IIV3)

Outcome Measures

Primary Outcome Measures :

1. Number of Participants From Each Arm Who Received Influenza Vaccine Vaccine [ Time Frame: Day 0 to 28 ]

Secondary Outcome Measures :

1. Number of Participants With Related Adverse Events [ Time Frame: Day 0 to 28 post-immunization ]

Other Outcome Measures:

1. Lymphocyte Response to Influenza Immunization [ Time Frame: Day 6-28 post-immunization ]
   Compare lymphocyte responses at Days 6-14 and the lymphocyte and serology responses at Day 28 post-immunization following annual administration of the influenza vaccines

Eligibility Criteria

• Ages Eligible for Study: 8 Years to 100 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Otherwise healthy, ambulatory children or adults, ages 8-17 years (identical twin pairs), 18-30 years (identical or fraternal twin pairs), 40-49 years (identical or fraternal twin pairs) or 70-100 years (twin or non-twin adults).
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. Negative urine pregnancy test for women of childbearing potential
6. If the subject is female and of childbearing potential, she must use an acceptable method of contraception and not become pregnant for the duration of the study. (Acceptable contraception includes implants, injectables, combined oral contraceptives, effective intrauterine devices (IUDs), sexual abstinence, or a vasectomized partner).

Exclusion Criteria:

1. Prior vaccination with TIV or LAIV in Fall 2009
2. Allergy to egg or egg products, or to vaccine components, including gentamicin, gelatin, arginine or MSG (for LAIV only), or thimerosal (TIV multidose vials only).
3. Life-threatening reactions to previous influenza vaccinations
4. Asthma (LAIV groups only)
5. Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
6. History of immune deficiency
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, blood pressure >150/95 at screening, or any other chronic disorder which, in the opinion of the investigator, might jeopardize volunteer safety or compliance with the protocol.
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 are permissible).
11. Subjects in close contact with anyone who has a severely weakened immune system should not receive LAIV.
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, Plavix, Aggrenox may be acceptable after review by investigator.
16. Receipt of blood or blood products within the past 6 months
17. Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol
18. Inactivated vaccine 14 days prior to vaccination
19. Live, attenuated vaccine within 60 days of vaccination
20. History of Guillain-Barre Syndrome
21. Pregnant or lactating woman
22. Use of investigational agents within 30 days prior to enrollment
23. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment
24. 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.

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Cornelia L Dekker, MD; Stanford University
• Principal Investigator: Mark M Davis, PhD; Stanford University
• Principal Investigator: Garry Nolan, PhD; Stanford University
• Principal Investigator: Ann Arvin, MD; Stanford University
• Principal Investigator: Stephen Quake, PhD; Stanford University

More Information

Additional Information:

Stanford LPCH Vaccine Program Clinical Trials Website 

Publications:

Horowitz A, Strauss-Albee DM, Leipold M, Kubo J, Nemat-Gorgani N, Dogan OC, Dekker CL, Mackey S, Maecker H, Swan GE, Davis MM, Norman PJ, Guethlein LA, Desai M, Parham P, Blish CA. Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry. Sci Transl Med. 2013 Oct 23;5(208):208ra145. doi: 10.1126/scitranslmed.3006702.

Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ, Furman D, Shen-Orr S, Dekker CL, Swan GE, Butte AJ, Maecker HT, Davis MM. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015 Jan 15;160(1-2):37-47. doi: 10.1016/j.cell.2014.12.020.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Cheung P, Vallania F, Warsinske HC, Donato M, Schaffert S, Chang SE, Dvorak M, Dekker CL, Davis MM, Utz PJ, Khatri P, Kuo AJ. Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging. Cell. 2018 May 31;173(6):1385-1397.e14. doi: 10.1016/j.cell.2018.03.079. Epub 2018 Apr 26.

• Responsible Party: Cornelia L. Dekker, Professor, Pediatrics, Stanford University
• ClinicalTrials.gov Identifier: NCT01987349
• Other Study ID Numbers: SU-17219-2009; 2U19AI057229-06 ( U.S. NIH Grant/Contract )
• First Posted: November 19, 2013
• Results First Posted: May 12, 2017
• Last Update Posted: May 12, 2017
• Last Verified: April 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Cornelia L. Dekker, Stanford University:

Influenza vaccines; healthy participants; immunity to influenza; identical twins; fraternal twins; non-twins

Additional relevant MeSH terms:

Influenza, Human; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases