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CompletedNCT03453801SLVP030Updated Feb 13, 2020

The Role of CD4+ Memory Phenotype, Memory, and Effector T Cells in Vaccination and Infection

A Phase 1 interventional study of Fluzone® and FluMist® in Influenza and Healthy, sponsored by Stanford University. Completed at 1 site in United States. Open to participants aged 6 Months to 10 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-02-13.

Sponsored by Stanford University · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
80
Allocation
Non-randomized
Ages
6 Months to 10 Years
Sex
All
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Study summary

The purpose of this study is provide a better understanding of the adaptive immune response to the licensed influenza vaccines in children.

Read the detailed description

This is a Phase I study of up to 100 healthy children, ages 6 months to 10 years of age, who will receive either Flumist® live, attenuated influenza virus vaccine, quadrivalent (LAIV4) or the current Fluzone® inactivated influenza vaccine, quadrivalent (IIV4). The volunteers will be enrolled into one of 3 Groups. Volunteers will return each year until 2018-2019 for annual flu immunizations and study visits. Questionnaires will be administered annually to record demographic characteristics, vaccination history, exposure to animals, day care and medically attended illness. There are no exclusions for gender, ethnicity or race.

Volunteers in the Non-twin Flu/MMRV naive group will also receive the measles, mumps, rubella and varicella (MMRV) vaccine at approximately 12-15 months of age (to be administered by the volunteers' personal pediatrician, not as a study vaccine). They will then come for a study visit to collect blood 60 days later.

Each twin is counted as a single participant. All reporting numbers reflect the number of participants, not the number of twin pairs.

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Conditions studied

  • Influenza
  • Healthy

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Keywords

  • Inactivated, influenza vaccine quadrivalent
  • Live, attenuated influenza vaccine quadrivalent
  • Young children
  • Identical twins
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Who can participate

Ages eligible
6 Months to 10 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Otherwise healthy non-twins 6 months - 10 years old, or 2-5 year old identical (MZ) twins.
  2. Willing to complete the informed consent process (including assent for minors 7 years old and above).
  3. Availability for follow-up for the planned duration of the study - annually until 2018-2019 influenza vaccination season
  4. Acceptable medical history by review of inclusion/exclusion criteria and vital signs.
  5. Non-twin flu/MMRV naive group: Willing to have primary care physician immunize child with the MMRV vaccine and return for a study visit approximately 60 days later.

Exclusion criteria

Exclusion Criteria:

  1. Prior off-study vaccination with the current year's seasonal influenza vaccine.
  2. Life-threatening reactions to previous influenza vaccinations
  3. Allergy to egg or egg products, or to vaccine components
  4. Active systemic or serious concurrent illness, including febrile illness on 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. Chronic Hepatitis B or C.
  8. 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)
  9. Malignancy
  10. 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.
  11. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
  12. Receipt of blood or blood products within the past 6 months or planned used during the study.
  13. Receipt of Inactivated vaccine 14 days prior to study enrollment, or planned vaccinations prior to completion of last study visit ( \~ 28 Day after study vaccination)
  14. Receipt of live, attenuated vaccine within 60 days prior to enrollment of planned vaccination prior to completion of last study visit (\~ 28 Day after study vaccination)
  15. Need for allergy immunization (that cannot be postponed) during the study period.
  16. History of Guillain-Barré syndrome
  17. Use of investigational agents within 30 days prior to enrollment or planned use during the study.
  18. 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.
  19. 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.
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Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
80 participants (actual)

Study arms

  • Experimental
    MZ twins 2-5 yo

    Monozygotic twins, 2-5 yo (annual return): In 2014-2015, individual twin participants will be given FluMist® a live, attenuated influenza vaccine quadrivalent (LAIV4) intranasally. Vaccine non-naive participants will return annually for flu immunization and for blood samples on Days 0, 7 and 60 post-immunization. Vaccine naive children will receive two immunizations in the first year, 28 days apart then return annually for flu immunization. Blood samples will be obtained on Days 0, 7 and 60 post second-immunization. Beginning in 2015-2016, participants in this arm will receive Fluzone® inactivated influenza vaccine quadrivalent (IIV4) as an intramuscular (IM) injection annually following Advisory Committee on Immunization Practices (ACIP) recommendation against LAIV4.

    Biological: Fluzone® · Biological: FluMist®

  • Experimental
    Non-twins 6 mo-10 yo

    Non-twins 6 mo-10 years (annual return): In 2014-2015, participants between 6-23 mo will be given Fluzone® inactivated influenza vaccine quadrivalent (IIV4) IM then switch to FluMist® a live, attenuated influenza vaccine quadrivalent (LAIV4) intranasally starting at age 24 months in annual follow-up. Participants aged 24 mo-8 yo will be given LAIV4 at enrollment and for annual follow-up. However, if LAIV4 is contraindicated, the child will continue with IIV4. Participants 9-10 yo will be given IIV4 annually. Vaccine non-naive participants will return annually for flu immunization and for blood samples on Days 0 and 60 post immunization. Vaccine naive children will get two doses of vaccine the first year then return annually for flu immunization and blood samples on Day 0 and 60 post second immunization. Beginning in 2015-2016, all participants in this arm will receive Fluzone® inactivated influenza vaccine quadrivalent (IIV4) annually following ACIP recommendation against LAIV4.

    Biological: Fluzone® · Biological: FluMist®

  • Experimental
    Non-twins 6-12 mo Flu/MMRV Naïve

    Non-twins 6-12 mo Flu/MMRV Naïve (annual return): In 2014-2015, participants 6-12 mo who are flu and MMRV naïve will be given Fluzone® inactivated influenza vaccine quadrivalent (IIV4) as an IM injection. In Year 1, participants will return for a second flu immunization at least 28 days later and for blood samples on Days 0 and 60 post-second immunization and on Day 60 post MMRV (to be given by primary care physician). In Years 2-5, participants will return annually for Fluzone® IIV4 flu immunization and for blood samples on Days 0 and 60 post-immunization.

    Biological: Fluzone®

Interventions

  • BiologicalFluzone®

    Fluzone® Quadrivalent (IIV4; inactivated influenza virus vaccine): The pediatric dose (6-35 months) will be supplied in a prefilled, single dose syringe, 0.25 mL (no preservative). Each 0.5 mL dose of Fluzone® Quadrivalent (36 months-adult) will be supplied in a prefilled, single dose syringe, 0.5 mL (no preservative). Both formulations given IM.

    Also known as: IIV4

  • BiologicalFluMist®

    FluMist® Quadrivalent: live, attenuated influenza virus vaccine quadrivalent, given by intranasal spray

    Also known as: LAIV4

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What researchers measure

Primary outcomes

  1. Frequency of antigen-specific T memory phenotype cells (TMP)

    The percentage of cells with the various antigen-specific T memory phenotypes will be determined.

    Time frame: Day 0 to Day 60

Secondary outcomes

  1. T cell receptor (TCR) repertoire analysis deep phenotyping by mass cytometry (CyTOF)

    The TCR repertoire encompasses the different sub-types of T-cell receptors of the immune system.

    Time frame: Day 0 to Day 60

  2. Deep phenotyping by mass cytometry (CyTOF)

    Deep phenotyping is the analysis of phenotypic abnormalities of the individual components of the phenotype.

    Time frame: Day 0 to Day 60

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Study locations

1 site
  • Stanford University
    Stanford, California 94304, United States
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References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

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Registry details

Key details

Study ID
NCT03453801
Lead sponsor
Stanford University
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Responsible party
Philip Grant (Assistant Professor of Medicine (Infectious Diseases), Stanford University) — Principal investigator
First posted
Mar 5, 2018
Start date
Sep 30, 2014
Primary completion
Jan 14, 2019
Completion
Jan 14, 2019
Last update
Feb 13, 2020

Study contacts

Cornelia L Dekker, MD
principal investigator · Stanford University
Mark M Davis, PhD
principal investigator · Stanford University
Philip M Grant, MD
principal investigator · Stanford University

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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