Genetic and Environmental Factors in the Response to Influenza Vaccination

Phase 1

Completed

• Conditions: Healthy; Influenza
• Interventions: Biological: FluMist® Quadrivalent; Biological: Fluzone® Quadrivalent vaccine

• Registration Number: NCT03088904
• Lead Sponsor: Stanford University

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.

Detailed Description

This is a phase 1 study of 120 healthy 12-49 year old adolescents and adult volunteers who are given licensed seasonal influenza vaccine. There are no exclusions for gender, ethnicity or race. The volunteers will be enrolled into one of 3 groups:

Group A: Up to 40 healthy monozygotic (MZ) twin volunteers, 12-49 years old, will be given inactivated influenza vaccine quadrivalent (IIV4). 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).

Group B: Up to 40 healthy dizygotic (DZ) twin volunteers, 12-49 years old, will be given inactivated influenza vaccine quadrivalent (IIV4). 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).

Group C: Up to 40 healthy monozygotic (MZ) twin volunteers, 12-49 years old, will be randomized within the twin pair to receive either inactivated influenza vaccine quadrivalent (IIV4) or live, attenuated influenza vaccine quadrivalent (LAIV4). 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 was reopened in 2018 with the availability of LAIV4.

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

Study Timeline

• Study Start: 2014-10-03
• Study First Submitted: 2017-03-17
• Study First Submitted QC: 2017-03-17
• Study First Posted: 2017-03-23
• Primary Completion: 2018-12-12
• Study Completion: 2018-12-12
• Status Verified: 2020-02
• Last Update Submitted: 2020-02-11
• Last Update Posted: 2020-02-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 109

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group C: MZ twins (IIV4 or LAIV4)	FluMist® Quadrivalent	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.
Group A: MZ twins (IIV4)	Fluzone® Quadrivalent vaccine	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).
Group B: DZ twins (IIV4)	Fluzone® Quadrivalent vaccine	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).
Group C: MZ twins (IIV4 or LAIV4)	Fluzone® Quadrivalent vaccine	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Sequencing of T-cell receptor (TCR)ab and Immunoglobulin Genes	Day 0 to Day 28	B and T cells will be sequenced for their antibody repertoires.
Natural Killer (NK) repertoire.	Day 0 to Day 28	Mass cytometry will be used to assess the NK cell repertoire.

Trial Locations

Locations (1)

Stanford University; 🇺🇸 Stanford, California, United States