T-cell And General Immune Response to Seasonal Influenza Vaccine (SLVP018) Year 3, 2011

• ClinicalTrials.gov Identifier: NCT03022422
• Recruitment Status: Completed
• First Posted: January 16, 2017
• Results First Posted: May 11, 2017
• Last Update Posted: August 21, 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 investigate markers, mechanisms and define general predictors for immunological health by comparing influenza vaccine responses in monozygotic and dizygotic twins.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: TIV; Biological: High-Dose TIV	Phase 4

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 B-E will receive a single administration of the 2011-2012 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. The number of individual participants, not the number of twin pairs is being reported in all the modules.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 63 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 3, 2011
• Study Start Date: September 2011
• Actual Primary Completion Date: December 2011
• Actual Study Completion Date: December 2011

Arms and Interventions

Arm	Intervention/treatment
Group B: 18-30 yo identical twins (TIV); Individual twins to receive Fluzone® standard TIV	Biological: TIV; Influenza Virus Vaccine Suspension for Intramuscular Injection; Other Name: Fluzone® TIV
Group C: 18-30 yo fraternal twins (TIV); Individual twins to receive Fluzone® standard TIV	Biological: TIV; Influenza Virus Vaccine Suspension for Intramuscular Injection; Other Name: Fluzone® TIV
Group D: 40-64 yo identical twins (TIV); Individual twins to receive Fluzone® standard TIV	Biological: TIV; Influenza Virus Vaccine Suspension for Intramuscular Injection; Other Name: Fluzone® TIV
Group E: 40-64 yo fraternal twins (TIV); Individual twins to receive Fluzone® standard TIV	Biological: TIV; Influenza Virus Vaccine Suspension for Intramuscular Injection; Other Name: Fluzone® TIV
Group F: 65-100 yo identical twins (TIV); Individual twins to receive Fluzone® standard TIV	Biological: TIV; Influenza Virus Vaccine Suspension for Intramuscular Injection; Other Name: Fluzone® TIV
Group F: 65-100 yo identical twins (High-Dose TIV); Individual twins to receive High-Dose Fluzone® TIV	Biological: High-Dose TIV; High-Dose Influenza Virus Vaccine supplied in a prefilled, single-dose syringe for intramuscular injection; Other Name: High-Dose Fluzone® TIV

Outcome Measures

Primary Outcome Measures :

1. Number of Individual Twins Who Received Influenza Vaccine [ Time Frame: Day 0 ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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 2011
2. Allergy to egg or egg products, or to vaccine components, including thimerosal (if TIV multidose vials used)
3. Allergy to latex (for Group F only - may be assigned to Fluzone High-Dose). Review with investigator.
4. Life-threatening reactions to previous influenza vaccinations
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 Visit 1
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 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.
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 aspirin up to 325 mg.day), Plavix, or Aggrenox must be reviewed by investigator to determine if this would affect the volunteer's safety.
16. Receipt of blood or blood products within the past 6 months
17. Medical or psychiatric condition or occupational responsibilities that preclude participant 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

Sponsors and Collaborators

Stanford University

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Cornelia Dekker, MD; Stanford University
• Principal Investigator: Mark 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

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.

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.

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.

de Bourcy CFA, Dekker CL, Davis MM, Nicolls MR, Quake SR. Dynamics of the human antibody repertoire after B cell depletion in systemic sclerosis. Sci Immunol. 2017 Sep 29;2(15):eaan8289. doi: 10.1126/sciimmunol.aan8289.

• Responsible Party: Cornelia L. Dekker, Professor, Pediatrics, Stanford University
• ClinicalTrials.gov Identifier: NCT03022422
• Other Study ID Numbers: SU-17219-2011; 2U19AI057229-06 ( U.S. NIH Grant/Contract )
• First Posted: January 16, 2017
• Results First Posted: May 11, 2017
• Last Update Posted: August 21, 2017
• Last Verified: August 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Cornelia L. Dekker, Stanford University:

Trivalent, inactivated influenza vaccine; High-Dose trivalent, inactivated influenza vaccine; Adult and elderly identical twins; Adult fraternal twins

Additional relevant MeSH terms:

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