Assessment of Viral Shedding Week Following Administration of Live Attenuated Influenza Vaccine in Children (FluSHED-2)

Assessment of Viral Shedding Week Following Administration of Live Attenuated Influenza Vaccine in Children: FluSHED-2 Study

LAIV shedding studies in children could be an important way to confirm whether impediments to viral replication do indeed explain these observed reductions in vaccine effectiveness (VE), whether prior vaccination has any influence on replication and what future implications (if any) this might have for the UK paediatric LAIV programme. LAIV virus replication in children will be dependent on virological and host factors. The virus factors include replicative fitness of individual strains and the susceptibility to inhibition by other replicating strains (ability to compete). Host factors which may influence this include pre-existing specific immunity as a result of prior infection or previous vaccination (with either LAIV or IIV), and innate immune factors including mucosal immunity.

There is significant variability in shedding across viral subtypes in studies done to date, so there is a need to obtain local data in a small pilot observational study which will look in detail at virus shedding by sequential daily virus samples, something not possible on a larger scale. The data generated will inform future LAIV studies in the UK in terms of optimum time of sample collection for viral shedding studies, which are likely to be required on a regular basis, to supplement field studies of vaccine effectiveness.

This study will enrol up to 30 children that will allow these factors to be assessed. Both written informed consent from parent/ guardian and written assent from the child will be in place prior to any study procedure. All participants will have a baseline assessment of pre--existing influenza immunity (blood test, oral fluid collection and nasal swabs), followed by a single dose of LAIV. Parents will then be asked to take nasal swabs at home on days 1, 2, 3, 4, 5, 6, 7, 8, with further nasal swab, blood test and oral fluid collection in hospital 4 weeks later, in order to assess for immune responses to LAIV.

Study Overview

• Status: Completed
• Conditions: Influenza Vaccines
• Intervention / Treatment: Biological: Live attenuated influenza vaccine (LAIV)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Imperial College Healthcare NHS Trust (St. Mary's Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 14 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Children age 6 years to 15 years +364 days of age on enrolment
• Children eligible to receive LAIV in accordance with current UK vaccine policy
• Written informed consent given by parent/ guardian and assent from child

Exclusion Criteria:

Contraindications to LAIV (notwithstanding allergy to egg protein), which include:

• Hypersensitivity to the active ingredients, gelatin or gentamicin (a possible trace residue)
• Previous systemic allergic reaction to LAIV
• Previous allergic reaction to an influenza vaccine (not LAIV) is a relative contra-indication, which must be discussed with the CI to confirm patient suitability
• Children/adolescents who are clinically immunodeficient due to conditions or immunosuppressive therapy such as: acute and chronic leukaemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high-dose corticosteroids*.
• Children / adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye's syndrome with salicylates and wild-type influenza infection.

• Pregnancy (determined by history). Where this cannot be confirmed, a urine pregnancy test will be performed.

  • High---dose steroids is defined as a treatment course for at least one month, equivalent to a dose greater than 20mg prednisolone per day (any age), or for children under 20kg, a dose greater than 1mg/kg/day.

NB: LAIV is not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled/low-dose oral systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All children; Administration of live attenuated influenza vaccine (LAIV)	Biological: Live attenuated influenza vaccine (LAIV); Single dose of LAIV; Other Names: Fluenz Tetra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type-specific Vaccine Virus Shedding in 2018/19 - Day 1 Post LAIV	No of participants with viral shedding on day 1 following LAIV vaccination	Assessed on day 1 post LAIV
Type-specific Vaccine Virus Shedding in 2018/19 - Day 2 Post LAIV	No of participants with viral shedding on day 2 following LAIV vaccination	Assessed on day 2 post LAIV
Type-specific Vaccine Virus Shedding in 2018/19 - Day 3 Post LAIV	No of participants with viral shedding on day 3 following LAIV vaccination	Assessed on day 3 post LAIV
Type-specific Vaccine Virus Shedding in 2018/19 - Day 4 Post LAIV	No of participants with viral shedding on day 4 following LAIV vaccination	Assessed on day 4 post LAIV
Type-specific Vaccine Virus Shedding in 2018/19 - Day 5 Post LAIV	No of participants with viral shedding on day 5 following LAIV vaccination	Assessed on day 5 post LAIV
Type-specific Vaccine Virus Shedding in 2018/19 - Day 6 Post LAIV	No of participants with viral shedding on day 6 following LAIV vaccination	Assessed on day 6 post LAIV
Type-specific Vaccine Virus Shedding in 2018/19 - Day 7 Post LAIV	No of participants with viral shedding on day 7 following LAIV vaccination	Assessed on day 7 post LAIV
Type-specific Vaccine Virus Shedding in 2018/19 - Day 8 Post LAIV	No of participants with viral shedding on day 8 following LAIV vaccination	Assessed on day 8 post LAIV

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantitative analysis of immunogenicity: serological	Haemagglutination inhibition (HAI) and Microneutralisation (MN) assay titres at each time point (day 0, 28) as well as ratios day 28/day 0 and proportions above thresholds and seroconverting	1 month
Quantitative analysis of immunogenicity: Oral fluids	Haemagglutination inhibition (HAI) titres in oral fluids at each time point (day 0, 28)	1 month
Quantitative analysis of immunogenicity: nasal IgA	Influenza-specific nasal IgA titres at each time point (day 0, 28)	1 month

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Public Health England
• Investigators: Principal Investigator: Paul J Turner, FRACP, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2018
• Primary Completion (Actual): April 1, 2019
• Study Completion (Actual): April 1, 2019

Study Registration Dates

• First Submitted: October 22, 2018
• First Submitted That Met QC Criteria: November 6, 2018
• First Posted (Actual): November 8, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: 18SM4658; 2018-002470-42 (EudraCT Number); 18/LO/1317 (Other Identifier: NHS HRA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No