Genetic and Environmental Factors in the Response to Influenza Vaccination

NCT03088904 | Completed Phase 1 FDA Drug

• 2 other identifiers: 310502U19AI057229-11
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate and compare the immune responses to influenza vaccination in monozygotic (identical) and dizygotic (fraternal) twins to determine the roles of genetics and environment in the response to flu vaccination.

Conditions

Influenza; Healthy

Keywords

Inactivated influenza vaccine quadrivalent; Live, attenuated influenza vaccine quadrivalent; Monozygotic twins; Dizygotic twins; Adults; Adolescents

Outcome Measures

Primary Outcomes (3)

• Hemagglutination inhibition (HAI) titers in response to influenza vaccination.

  Day 0 to Day 28

• Interferon-gamma (IFN-γ) production by T cells

  Day 0 to Day 28

• IFN-γ production by Natural Killer (NK) cells.

  Day 0 to Day 28

Secondary Outcomes (2)

• Sequencing of T-cell receptor (TCR)ab and Immunoglobulin Genes

  Day 0 to Day 28

• Natural Killer (NK) repertoire.

  Day 0 to Day 28

Study Arms (3)

Group A: MZ twins (IIV4)

EXPERIMENTAL

Group A: Up to 40 healthy monozygotic (MZ) individual twin volunteers, 12-49 years old, will be given inactivated influenza vaccine quadrivalent (IIV4) Fluzone® Quadrivalent vaccine. Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), Day 6-8 and Day 28+7 post-immunization. All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

Biological: Fluzone® Quadrivalent vaccine

Group B: DZ twins (IIV4)

EXPERIMENTAL

Group B: Up to 40 healthy dizygotic (DZ) individual twin volunteers, 12-49 years old, will be given inactivated influenza vaccine quadrivalent (IIV4) Fluzone® Quadrivalent vaccine. Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), and Day 6-8 and Day 28+ 7 (post-immunization). All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs).

Biological: Fluzone® Quadrivalent vaccine

Group C: MZ twins (IIV4 or LAIV4)

EXPERIMENTAL

Group C: Up to 40 healthy monozygotic (MZ) individual twin volunteers, 12-49 years old, will be randomized within the twin pair to receive either inactivated influenza vaccine quadrivalent (IIV4) Fluzone® Quadrivalent vaccine or live, attenuated influenza vaccine quadrivalent (LAIV4) FluMist® Quadrivalent. Each volunteer will complete a total of 3 visits: Day 0 (pre-immunization), Day 6-8 and Day 28+7 post-immunization. All visits will consist of drawing blood for study assays and monitoring for serious adverse events (SAEs). This group was terminated in 2016 due to ACIP recommendations against the use of LAIV but may be reopened in 2018 pending LAIV4 availability.

Biological: FluMist® Quadrivalent; Biological: Fluzone® Quadrivalent vaccine

Interventions

FluMist® Quadrivalent BIOLOGICAL

LAIV4 vaccine dosage is 0.2 mL. Vaccine will be administered as an intranasal spray. Each sprayer contains a single dose of FluMist® Quadrivalent; approximately one-half of the contents should be administered into each nostril. 0.1 mL (i.e., half of the dose from a single FluMist sprayer) is administered into each nostril while the recipient is in an upright position. Insert the tip of the sprayer just inside the nose and rapidly depress the plunger until the dose-divider clip stops the plunger. The dose divider clip is removed from the sprayer to administer the second half of the dose (0.1 mL) into the other nostril.

Group C: MZ twins (IIV4 or LAIV4)

Fluzone® Quadrivalent vaccine BIOLOGICAL

IIV4 vaccine will be administered as a 0.5 mL dose, with a sterile, disposable syringe and needle by IM injection into the deltoid muscle.

Group A: MZ twins (IIV4); Group B: DZ twins (IIV4); Group C: MZ twins (IIV4 or LAIV4)

Eligibility Criteria

• Age: 12 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Otherwise healthy, 12-49 years old, identical (MZ) or fraternal (DZ) twins.
• Willing to complete the informed consent process (including assent for minors 12-17 years of age, inclusive).
• Availability for follow-up for the planned duration of the study at least 28 days after immunization.

You may not qualify if:

• Prior off-study vaccination with the current year's seasonal influenza vaccine.
• Allergy to egg or egg products, or to vaccine components, (including gentamicin, gelatin, arginine or MSG in LAIV)
• Life-threatening reactions to previous influenza vaccinations.
• Asthma (If yes, not eligible for Group C).
• 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.
• Blood pressure \>150 systolic or \>95 diastolic at first study visit and the day of vaccination.
• Hospitalization in the past year for congestive heart failure or emphysema.
• 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).
• In close contact with anyone who has a severely weakened immune system and requires a protective environment (If yes, may be ineligible for Group C; exposure to such persons should be avoided for 7 days after receipt of LAIV).
• 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).
• 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.

Sponsors & Collaborators

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

Study Sites (1)

Stanford University

Stanford, California, 94305-5208, United States

Location

Related Links

• Stanford-LPCH Vaccine Program Stanford University School of Medicine

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Study Officials

• Mark M Davis, PhD

  Stanford School of Medicine, Dept. of Microbiology and Immunology

  PRINCIPAL INVESTIGATOR

• Catherine Blish, MD

  Stanford School of Medicine, Dept. of Medicine

  PRINCIPAL INVESTIGATOR

• William Robinson, MD

  Stanford School of Medicine, Dept. of Medicine

  PRINCIPAL INVESTIGATOR

• Cornelia Dekker, MD

  Stanford School of Medicine, Dept. of Pediatrics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: 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: March 17, 2017
• First Posted: March 23, 2017
• Study Start: October 3, 2014
• Primary Completion: December 12, 2018
• Study Completion: December 12, 2018
• Last Updated: February 13, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)