The Effect of Live Attenuated Inactivated Influenza Vaccine on Experimental Human Pneumococcal Carriage Study (LAIV/EHPC)

April 10, 2018 updated by: Liverpool University Hospitals NHS Foundation Trust

The investigators are interested in examining the effect of the Live Attenuated Influenza (flu) Vaccine (LAIV) upon nasal carriage of bacteria called Streptococcus pneumoniae (also known as pneumococcus). The nasal spray is a live attenuated vaccine which means that it has weakened virus that does not cause disease. This vaccine is licenced in the United Kingdom for children and adolescents from 2 to 18 years of age.

Pneumococcus can commonly be found harmlessly inhabiting the nose where it does not cause any problem (pneumococcal colonisation). About 10% of adults carry pneumococcus at any one time, and almost all adults experience an episode of carriage at least once per year. Carriage acts as a natural vaccine, boosting immunity against pneumococcal infection in adults and children.

During influenza there is an increase in the burden of pneumococcal pneumonia. We have studied the effects of pneumococcus for many years and have developed a programme in which we can nasally inoculate healthy participants with a dose of pneumococcus and achieve a reproducible carriage rate. The investigators would now like to use this model to investigate the effects of the nasal influenza vaccine upon pneumococcal carriage and to better understand how influenza infections lead to increased susceptibility to pneumonia.

Pneumococcal disease in young adults is rare - less than 10 cases per 100,000 people per year. When pneumococcus does cause problems, usually in young children or elderly people, it can be very serious as it is responsible for diseases such as pneumonia, sepsis and meningitis, which kill millions of children around the world each year.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Secondary bacterial infections such as pneumococcal pneumonia are a leading cause of death during influenza endemics. Individuals recently infected with influenza become more susceptible to pneumonia, an effect associated with increased density of pneumococcal carriage in the nose and uncontrolled inflammatory immunological responses. The interaction of influenza virus and pneumococcus has been known and well documented. Recent works have shown that the Live Attenuated Influenza Vaccine (LAIV) enhances pneumococcal carriage in murine models. These results highlighted the potential effect of mass immunization of children with LAIV on pneumococcal carriage. Increased carriage could lead to increased pneumococcal disease in LAIV-vaccinated individuals as well as increased bacterial transmission within the population. LAIV has been licensed for use in children since 2011 in Europe, and has been increasingly administered in children and adults in the USA. There is an urgent need for a clinical trial that will determine the effect of LAIV on pneumococcal carriage dynamics.

The investigators have developed a safe and reproducible experimental human pneumococcal carriage (EHPC) model. The investigators will use EHPC to define the effect of antecedent and concurrent LAIV on pneumococcal carriage acquisition, density and duration. The investigators will perform two double - blinded Randomised Controlled Trials (RCT) to compare LAIV with Quadrivalent Inactivated Influenza Vaccine (QIV). The investigators will compare clinical symptoms, pneumococcal carriage density and duration associated with both vaccines administered antecedent to or concurrently with EHPC inoculation. Changes in the nasopharyngeal microbiome, inflammatory responses in the nasal mucosal and lung cellular immunity associated with influenza virus and pneumococcus interaction will be investigated. This project may provide some reassurance regarding the impact of mass immunization with LAIV on carriage or, if carriage is increased, will provide knowledge of how a natural carriage episode might develop into pneumonia in susceptible subjects during pandemic influenza.

Study Type

Interventional

Enrollment (Actual)

324

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
    • Merseyside
      • Liverpool, Merseyside, United Kingdom, L7 8XP
        • Royal Liverpool Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • have capacity to give informed consent
  • aged 18-50 yrs - ages chosen to minimise the risk of pneumococcal infection
  • speak fluent English- to ensure a comprehensive understanding of the research project and their proposed involvement, in order to minimise any communication issues to maximise participant safety.

Exclusion Criteria:

  • currently involved in another study unless observational or in follow-up phase (non-interventional)
  • received any influenza vaccine in the last 2 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Study One: LAIV + Inoculation
LAIV Nasal Spray: Inoculation (FLUMIST or FLUENZ) plus intramuscular placebo then inoculation with pneumococci bacteria
Biological: Study one: LAIV + Inoculation
Pneumococci bacteria nasal inoculation following vaccination with LAIV and intramuscular placebo
Other Names:
  • FLUMIST or FLUENZ AstraZeneca
Placebo Comparator: Study One: Placebo + inoculation
Quadrivalent Inactivated Influenza Vaccine Intramuscular (Fluarix Tetra) plus nasal placebo then inoculation with pneumococci bacterial
Biological: Study one: Placebo + Inoculation
Pneumococci bacteria nasal inoculation following vaccination QIV with nasal placebo spray
Other Names:
  • Fluarix Tetra GlaxoSmithKline
Active Comparator: Study Two: Inoculation + LAIV
Inoculation with pneumococci bacteria then Live attenuated Influenza Vaccine Nasal Spray (FLUMIST or FLUENZ) plus intramuscular placebo
Biological: Study two: Inoculation + LAIV
Pneumococci bacteria nasal inoculation prior to vaccination with LAIV and intramuscular placebo
Other Names:
  • FLUMIST or FLUENZ AstraZeneca
Placebo Comparator: Study Two: Inoculation + placebo
Inoculation with pneumococci bacteria then Quadrivalent Inactivated Influenza Vaccine Intramuscular (Fluarix Tetra) plus nasal placebo
Biological: Study two: Inoculation + placebo
Pneumococci bacteria nasal inoculation prior to vaccination QIV with nasal placebo
Other Names:
  • Fluarix Tetra GlaxoSmithKline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Detection of pneumococcal bacteria in the nasal wash sample
Time Frame: within 6 weeks of inoculation per patient
Primary outcome: detection of pneumococcal bacteria in the nasal wash sample at any time point after inoculation by classical microbiology. 130 participants will complete the study (65 in each arm) to achieve 80% power to detect 50% increase in colonisation rates induced by antecedent LAIV compared to control
within 6 weeks of inoculation per patient

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Liverpool University Hospitals NHS Foundation Trust

Collaborators

Liverpool School of Tropical Medicine
Sponsor GmbH

Investigators

  • Principal Investigator: Jamie Rylance, Liverpool School of Tropical Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2015

Primary Completion (Actual)

May 1, 2017

Study Completion (Actual)

May 1, 2017

Study Registration Dates

First Submitted

October 18, 2016

First Submitted That Met QC Criteria

April 10, 2018

First Posted (Actual)

April 18, 2018

Study Record Updates

Last Update Posted (Actual)

April 18, 2018

Last Update Submitted That Met QC Criteria

April 10, 2018

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 4896

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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