Adaptive Immune Responses and Repertoire in Influenza Vaccination and Infection (SLVP031)

• ClinicalTrials.gov Identifier: NCT03028987
• Recruitment Status: Terminated
• First Posted: January 23, 2017
• Results First Posted: September 12, 2017
• Last Update Posted: September 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:

The purpose of this study is provide a better understanding of the adaptive immune response to the licensed flu vaccines. The investigators hope the information learned from this study will help identify and describe important factors of influenza immunity especially of or specific proteins associated with the T-cell immune response.

Condition or disease	Intervention/treatment	Phase
Influenza	Biological: Fluzone®; Biological: FluMist®	Phase 4

Detailed Description:

This is a study of up to 20 healthy monozygotic (MZ) twins, 18-49 years old, that are participants from past Stanford-LPCH Vaccine Program trials and who have been identified as human leukocyte antigen (HLA) DR1501+ or DR0701+ by lab assay results. Volunteers will be contacted to assess interest in participating in this study. Both twins in the pair must be willing to participate in the study. All participants will be randomized within the twin pair to receive either the seasonal live, attenuated influenza vaccine (LAIV) or the seasonal quadrivalent inactivated influenza vaccine (IIV4). Immunization will be at Day 0, blood samples for immunogenicity assays will be collected prior to immunization and at Days 7 (6-8) and 28 (24-32).

This study was halted due to the Advisory Committee on Immunization Practices decision not to recommend use of LAIV.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Project 1. The Role of CD4+ Memory Phenotype, Memory, and Effector T-Cells in Vaccination and Infection - Influenza-specific DR1501+ and DR0701+ T-cells
• Actual Study Start Date: November 19, 2014
• Actual Primary Completion Date: November 18, 2015
• Actual Study Completion Date: November 18, 2015

Arms and Interventions

Arm	Intervention/treatment
LAIV randomized; Volunteers are past participants who have been identified as HLA DR1501+ or DR0701+ by lab assay results. All participants will be randomized within the twin pair to receive either the seasonal quadrivalent live, attenuated influenza vaccine (LAIV4)/ FluMist® or the seasonal quadrivalent inactivated influenza vaccine (IIV4)/ Fluzone® .	Biological: FluMist®; FluMist® Intranasal Spray (quadrivalent, live, attenuated influenza vaccine)
IIV4 randomized; Volunteers are past participants who have been identified as HLA DR1501+ or DR0701+ by lab assay results. All participants will be randomized within the twin pair to receive either the seasonal quadrivalent live, attenuated influenza vaccine (LAIV4)/ FluMist® or the seasonal quadrivalent inactivated influenza vaccine (IIV4)/ Fluzone®	Biological: Fluzone®; Fluzone® Quadrivalent (IIV4; inactivated influenza virus vaccine)

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Who Received Influenza Vaccine [ Time Frame: Day 0 ]
   Number of individual twins who received either LAIV or IIV4 as dictated by their group assignment

Secondary Outcome Measures :

1. Number of Participants With Related Adverse Events [ Time Frame: Day 0 to 28 post-immunization ]
   Number of individual twins who experienced related adverse events through the course of the study.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 49 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Otherwise healthy 18-49 years old identical (MZ) twins identified as DR1501+ or DR0701+ by lab assay results. Both twins in the pair must be willing to participate in the study.
2. Willing to complete the informed consent process
3. Availability for follow-up for the planned duration of the study
4. Acceptable medical history by review of inclusion/exclusion criteria and vital signs.

Exclusion Criteria:

1. Prior off-study vaccination with the current year's seasonal influenza vaccine.
2. Allergy to egg or egg products or to vaccine components including gentamicin, gelatin, arginine or MSG
3. Life-threatening reactions to previous influenza vaccinations
4. Asthma (a contraindication for receipt of LAIV4)
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 first study visit and the day of vaccination.
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 systemic glucocorticoids (corticosteroid nasal sprays and topical steroids are permissible in all groups; inhaled steroid use is not permissible)
12. Participants who care for severely immunosuppressed persons that require a protective environment should not receive LAIV, or should avoid contact with such persons for 7 days after receipt, given the theoretical risk for transmission of the live attenuated vaccine virus to close contacts. [If yes, may be ineligible]
13. 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).
14. 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.
15. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
16. Use of any anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet agents such as aspirin (except up to 325 mg. per day), Plavix, or Aggrenox must be reviewed by investigator to determine if this would affect the volunteer's safety.
17. Has taken an influenza antiviral medication within 48 hours prior to study vaccination [If yes, may not eligible if unable to schedule at an appropriate interval].
18. Receipt of blood or blood products within the past 6 months or planned used during the study.
19. Medical or psychiatric condition or occupational responsibilities that preclude participant compliance with the protocol
20. Receipt of an inactivated vaccine 14 days prior to study enrollment, or planned vaccinations prior to completion of last study visit ( ~ 28 days after study vaccination)
21. Receipt of a live, attenuated vaccine within 60 days prior to enrollment of planned vaccination prior to completion of last study visit (~ 28 days after study vaccination)
22. Need for allergy immunization (that cannot be postponed) during the study period.
23. History of Guillain-Barré syndrome
24. Pregnant or lactating woman
25. Use of investigational agents within 30 days prior to enrollment or planned use during the study.
26. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment or planned donation prior to completion of the last visit.
27. 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 Dekker, MD; Stanford University
• Principal Investigator: Mark Davis, PhD; Stanford University
• Principal Investigator: K. Christopher Garcia, PhD; Stanford University

More Information

• Responsible Party: Cornelia L. Dekker, Professor, Pediatrics, Stanford University
• ClinicalTrials.gov Identifier: NCT03028987
• Other Study ID Numbers: SU-31434-2014-2019; 2U19AI057229-11 ( U.S. NIH Grant/Contract )
• First Posted: January 23, 2017
• Results First Posted: September 12, 2017
• Last Update Posted: September 12, 2017
• Last Verified: July 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Cornelia L. Dekker, Stanford University:

Quadrivalent, inactivated influenza vaccine; Quadrivalent, live, attenuated influenza vaccine; Identical twin adults

Additional relevant MeSH terms:

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