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

NCT03453801 | Completed Phase 1 FDA Drug

• 2 other identifiers: SU-31256U19AI057229-11
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Influenza; Healthy

Keywords

Inactivated, influenza vaccine quadrivalent; Live, attenuated influenza vaccine quadrivalent; Young children; Identical twins

Outcome Measures

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.

  Day 0 to Day 60

Secondary Outcomes (2)

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

  Day 0 to Day 60

• Deep phenotyping by mass cytometry (CyTOF)

  Day 0 to Day 60

Study Arms (3)

MZ twins 2-5 yo

EXPERIMENTAL

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®

Non-twins 6 mo-10 yo

EXPERIMENTAL

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®

Non-twins 6-12 mo Flu/MMRV Naïve

EXPERIMENTAL

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

Fluzone® BIOLOGICAL

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

MZ twins 2-5 yo; Non-twins 6 mo-10 yo; Non-twins 6-12 mo Flu/MMRV Naïve

FluMist® BIOLOGICAL

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

Also known as: LAIV4

MZ twins 2-5 yo; Non-twins 6 mo-10 yo

Eligibility Criteria

• Age: 6 Months - 10 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Otherwise healthy non-twins 6 months - 10 years old, or 2-5 year old identical (MZ) twins.
• Willing to complete the informed consent process (including assent for minors 7 years old and above).
• Availability for follow-up for the planned duration of the study - annually until 2018-2019 influenza vaccination season

You may not qualify if:

• 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.
• Prior off-study vaccination with the current year's seasonal influenza vaccine.
• Life-threatening reactions to previous influenza vaccinations
• Allergy to egg or egg products, or to vaccine components
• Active systemic or serious concurrent illness, including febrile illness on the day of vaccination
• History of immunodeficiency (including HIV infection)
• 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.
• Chronic Hepatitis B or C.
• 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)
• Malignancy
• 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.
• History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular medical follow up or hospitalization during the preceding year
• Receipt of blood or blood products within the past 6 months or planned used during the study.
• 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)
• 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)

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Stanford University

Stanford, California, 94304, United States

Location

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines; FluMist

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Cornelia L Dekker, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Mark M Davis, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

• Philip M Grant, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine (Infectious Diseases)

Study Record Dates

• First Submitted: February 27, 2018
• First Posted: March 5, 2018
• Study Start: September 30, 2014
• Primary Completion: January 14, 2019
• Study Completion: January 14, 2019
• Last Updated: February 13, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)