The Effect of Live Attenuated Inactivated Influenza Vaccine on Experimental Human Pneumococcal Carriage Study

NCT03502291 | Completed Phase 4 DMC

• 1 other identifier: 4896
• Study Type: interventional
• Target: 324
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pneumonia; Influenza, Human

Keywords

Human challenge models; Immunity; Streptococcus pneumoniae; Live Attenuated Influenza Vaccine

Outcome Measures

Primary Outcomes (1)

• Detection of pneumococcal bacteria in the nasal wash sample

  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

Study Arms (4)

Study One: LAIV + Inoculation

ACTIVE COMPARATOR

LAIV Nasal Spray: Inoculation (FLUMIST or FLUENZ) plus intramuscular placebo then inoculation with pneumococci bacteria

Biological: Study one: LAIV + Inoculation

Study One: Placebo + inoculation

PLACEBO COMPARATOR

Quadrivalent Inactivated Influenza Vaccine Intramuscular (Fluarix Tetra) plus nasal placebo then inoculation with pneumococci bacterial

Biological: Study one: Placebo + Inoculation

Study Two: Inoculation + LAIV

ACTIVE COMPARATOR

Inoculation with pneumococci bacteria then Live attenuated Influenza Vaccine Nasal Spray (FLUMIST or FLUENZ) plus intramuscular placebo

Biological: Study two: Inoculation + LAIV

Study Two: Inoculation + placebo

PLACEBO COMPARATOR

Inoculation with pneumococci bacteria then Quadrivalent Inactivated Influenza Vaccine Intramuscular (Fluarix Tetra) plus nasal placebo

Biological: Study two: Inoculation + placebo

Interventions

Study one: LAIV + Inoculation BIOLOGICAL

Pneumococci bacteria nasal inoculation following vaccination with LAIV and intramuscular placebo

Also known as: FLUMIST or FLUENZ AstraZeneca

Study One: LAIV + Inoculation

Study one: Placebo + Inoculation BIOLOGICAL

Pneumococci bacteria nasal inoculation following vaccination QIV with nasal placebo spray

Also known as: Fluarix Tetra GlaxoSmithKline

Study One: Placebo + inoculation

Study two: Inoculation + LAIV BIOLOGICAL

Pneumococci bacteria nasal inoculation prior to vaccination with LAIV and intramuscular placebo

Also known as: FLUMIST or FLUENZ AstraZeneca

Study Two: Inoculation + LAIV

Study two: Inoculation + placebo BIOLOGICAL

Pneumococci bacteria nasal inoculation prior to vaccination QIV with nasal placebo

Also known as: Fluarix Tetra GlaxoSmithKline

Study Two: Inoculation + placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Liverpool University Hospitals NHS Foundation Trust: lead
• Sponsor GmbH: collaborator
• Liverpool School of Tropical Medicine: collaborator

Study Sites (1)

Royal Liverpool Hospital

Liverpool, Merseyside, L7 8XP, United Kingdom

Location

Related Publications (1)

• Mitsi E, Reine J, Urban BC, Solorzano C, Nikolaou E, Hyder-Wright AD, Pojar S, Howard A, Hitchins L, Glynn S, Farrar MC, Liatsikos K, Collins AM, Walker NF, Hill HC, German EL, Cheliotis KS, Byrne RL, Williams CT, Cubas-Atienzar AI, Fletcher TE, Adams ER, Draper SJ, Pulido D, Beavon R, Theilacker C, Begier E, Jodar L, Gessner BD, Ferreira DM. Streptococcus pneumoniae colonization associates with impaired adaptive immune responses against SARS-CoV-2. J Clin Invest. 2022 Apr 1;132(7):e157124. doi: 10.1172/JCI157124.

  PMID: 35139037 DERIVED

MeSH Terms

Conditions

Pneumonia; Influenza, Human

Interventions

Vaccination; FluMist

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Immunotherapy, Active; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques; Primary Prevention; Preventive Health Services; Health Services; Health Care Facilities Workforce and Services; Communicable Disease Control; Public Health Practice; Public Health; Environment and Public Health

Study Officials

• Jamie Rylance

  Liverpool School of Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Physical blind folds worn by participant. Unblinded research nurses to deliver the vaccines
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: DBRCT performed as two studies over two flu seasons. 2 arms to each study.

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: April 18, 2018
• Study Start: August 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2017
• Last Updated: April 18, 2018

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)