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

NCT ID: NCT03022435

Last Updated: 2017-05-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2013-01-31

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.

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.

Conditions

Influenza

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Group B: 18-30 yo identical twins (LAIV)

Participants to receive FluMist® LAIV by nasal spray.

Group Type: OTHER

LAIV

Intervention Type: BIOLOGICAL

Live, attenuated influenza vaccine for Intranasal Spray

Group B: 18-30 yo identical twins (TIV)

Participants to receive Fluzone® standard TIV

Group Type: OTHER

TIV

Intervention Type: BIOLOGICAL

Influenza Virus Vaccine Suspension for Intramuscular Injection

Group D: 40-64 yo identical twins (TIV)

Participants to receive Fluzone® standard TIV

Group Type: OTHER

TIV

Intervention Type: BIOLOGICAL

Influenza Virus Vaccine Suspension for Intramuscular Injection

Group F: 65-100 yo identical twins (TIV)

Participants to receive Fluzone® standard TIV

Group Type: OTHER

TIV

Intervention Type: BIOLOGICAL

Influenza Virus Vaccine Suspension for Intramuscular Injection

Group F: 65-100 yo identical twins (High-Dose TIV)

Participants to receive High-Dose Fluzone® standard TIV

Group Type: OTHER

High-Dose TIV

Intervention Type: BIOLOGICAL

High-Dose Influenza Virus Vaccine supplied in a prefilled, single-dose syringe

Interventions

TIV

Influenza Virus Vaccine Suspension for Intramuscular Injection

Intervention Type: BIOLOGICAL

High-Dose TIV

High-Dose Influenza Virus Vaccine supplied in a prefilled, single-dose syringe

Intervention Type: BIOLOGICAL

LAIV

Live, attenuated influenza vaccine for Intranasal Spray

Intervention Type: BIOLOGICAL

Other Intervention Names

Fluzone® standard TIV; High-Dose Fluzone® TIV; FluMist®

Eligibility 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 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Stanford University

OTHER

Sponsor Role: lead

Responsible Party

Cornelia L. Dekker

Professor, Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cornelia Dekker, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Mark Davis, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Garry Nolan, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Ann Arvin, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Stephen Quake, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

References

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.

Reference Type: BACKGROUND

PMID: 25246558 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25203448 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25740957 (View on PubMed)

Other Identifiers

2U19AI057229-06

Identifier Type: NIH

Identifier Source: secondary_id

View Link

SU-17219-2012

Identifier Type: -

Identifier Source: org_study_id