FluPRINT Study: Characterisation of the Immune and Transcriptional Response to LAIV

NCT04222595 | Completed

• 1 other identifier: FluPRINT Study OVG 2018/04
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

In 2013 the UK government introduced the nasal flu spray vaccine (Fluenz Tetra®) for use in children from 24 months to less than 18 years of age. This is a licensed vaccine that is safe, effective and like the injectable vaccine, needs to be given yearly. There is evidence that the nasal spray flu vaccine can offer better protection for children than the injectable flu vaccine but it is not yet fully understood why this is so. When the immune system responds to an infection or a vaccine, specific 'immune response' genes are activated or 'switched on'. This process is called gene expression and different types of immune responses cause the activation of different genes.This study is looking at how specific parts of the immune system like B and T cells respond to the nasal spray vaccine and how and what genes are activated by the vaccine. B cells make antibodies, a part of our immune system that helps to protect against invaders such as viruses or bacteria. The next time our bodies are exposed to the same invader, our B cells make antibodies that can recognise and stop the invader going on to cause an infection. Our T cells can help B cells to make antibodies and also help to direct the body to attack the invader instead of causing harm to healthy cells.

Conditions

Immunization

Outcome Measures

Primary Outcomes (3)

• To assess the change in molecular signature from baseline to day 28 after LAIV vaccination

  To assess gene expression differences between participants at baseline and day 28 after vaccination.

  Baseline and day 28 after vaccination

• To assess the change in immunological signature from baseline to day 28 after LAIV vaccination

  To assess differences in the phenotype and frequency of immune cell subsets analyzed by 40-antibody panel mass cytometry between participants at baseline and day 28 after vaccination.

  Baseline and day 28 after vaccination

• To assess the change in HAI antibody titer from baseline to day 28 after LAIV vaccination

  Percentage of participants with a 4 fold rise in HAI titre between the baseline sample and sample taken on day 28 after vaccination and percentage of participants with the HAI titer above 40.

  Baseline and day 28 after vaccination

Secondary Outcomes (2)

• To assess the change in functionality of the adaptive immune responses to LAIV from baseline to day 28 after LAIV vaccination

  Baseline and day 28 after vaccination

• To analyze the change in the influenza-specific T-cell repertoire (TCR) from baseline to day 28 after LAIV vaccination

  Baseline and day 28 after vaccination

Study Arms (4)

1- naive

NO INTERVENTION

Group 1: up to 10 children aged 4-6 years that never received LAIV before.

2- Fluenz Tetra nasal spray suspension

ACTIVE COMPARATOR

Group 2: up to 10 children aged 4-6 years that received LAIV once before. Single dose vaccine, administered as a nasal spray (0.2 ml administered as 0.1 ml per nostril).

Other: Fluenz Tetra nasal spray suspension

3- Fluenz Tetra nasal spray suspension

ACTIVE COMPARATOR

Group 3: up to 10 children aged 4-6 years that were vaccinated twice before.Single dose vaccine, administered as a nasal spray (0.2 ml administered as 0.1 ml per nostril).

Other: Fluenz Tetra nasal spray suspension

4- Fluenz Tetra nasal spray suspension

ACTIVE COMPARATOR

Group 4: up to 10 children aged 4-6 years that were vaccinated 3 or 4 times before.Single dose vaccine, administered as a nasal spray (0.2 ml administered as 0.1 ml per nostril).

Other: Fluenz Tetra nasal spray suspension

Interventions

Fluenz Tetra nasal spray suspension OTHER

Prophylaxis of influenza in children and adolescents from 24 months to less than 18 years of age. Single dose vaccine, administered as a nasal spray (0.2 ml administered as 0.1 ml per nostril).

Also known as: Influenza vaccine (live attenuated, nasal)

2- Fluenz Tetra nasal spray suspension; 3- Fluenz Tetra nasal spray suspension; 4- Fluenz Tetra nasal spray suspension

Eligibility Criteria

• Age: 48 Months - 72 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• The investigator believes that the parents/LAR(s) of the child can and will comply with requirements of the protocol (e.g. understanding of study procedure, consent process, availability at visits).
• Written informed consent obtained from parent(s)/LAR(s) of the subject
• Age from 4y+ 1day up to 6 years (until the day they turn 7y) at time of V1 (first immunisation visit)
• Born to two white Caucasian (of European descent) parents
• Participant is healthy as determined by general health assessment
• Have received all the vaccines specified in the UK immunisation schedule
• Group 1: Never received the intranasal flu vaccine before
• Group 2: Must have had at least 1 dose of the intranasal flu vaccine
• Group 3: Must have had at least 2 doses of the intranasal flu vaccine
• Group 4 : Must have had at least 3 or 4 doses of the internasal flu vaccine

You may not qualify if:

• Use (or planned use) of any non-registered or investigational product in 30 days before or after study vaccination
• Chronic serious medical conditions which may, in the opinion of the investigator, interfere with evaluation of study objectives e.g. chronic lung disease, chronic liver/renal disease, chronic renal failure chronic heart disease, congenital genetic syndromes (e.g. Trisomy 21).
• Recommended for inactivated influenza vaccine in UK (e.g. Children in clinical risk groups as specified by Public Health England) according to the Green Book, DoH.
• Meets any contraindications to vaccination as outlined in the Green Book, DoH
• Suspected or confirmed immunosuppressive or immunodeficiency conditions (including splenic dysfunction \& HIV)
• Autoimmune conditions (e.g. Type 1/2 diabetes mellitus, thyroid disease, juvenile idiopathic arthritis) and bleeding disorders
• Use of systemic steroids for more than one week e.g. prednisolone \>0.5mg/kg/day in the three months prior to first study intervention
• Chronic administration (≥14 days in total) of immunosuppressant's or other immune modifying drugs in the 3 months prior to first study intervention
• Receipt of blood, blood products and/or plasma derivatives or any immunoglobulin preparation in the three months prior to first study intervention
• Participants who have experienced fever (≥38.0°C) or coryzal symptoms within the 24 hours prior to first study intervention
• Actively wheezing or increased bronchodilators in the previous 72 hours prior to first study intervention
• Immunisation with inactivated vaccines within the week prior to first study intervention, or live vaccines within the three weeks prior to first study intervention
• Receipt of antipyretics within six hours prior to immunisation

Sponsors & Collaborators

• University of Oxford: lead
• European Commission: collaborator
• Stanford University: collaborator

Study Sites (1)

Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

MeSH Terms

Interventions

Influenza Vaccines

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Andrew Pollard, FRCPCH

  University of Oxford

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label study of healthy and immunocompetent children aged 4 to 6 years

Study Record Dates

• First Submitted: October 17, 2018
• First Posted: January 10, 2020
• Study Start: October 16, 2019
• Primary Completion: December 1, 2021
• Study Completion: June 27, 2022
• Last Updated: June 30, 2022

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)