A randomised, controlled, laboratory observer-blind, phase 3 trial to evaluate the effects of maternal or neonatal pneumococcal conjugate vaccination on pneumococcal carriage in infants up to nine months of age

Lead Research Organisation: MRC Unit, The Gambia

Abstract

A bacteria (or germ) called pneumococcus, which causes pneumonia, meningitis and blood stream infections, is responsible for hundreds of thousands of deaths as well as a tremendous burden of serious disease in babies and children each year. Children are already vaccinated against the infection at around 2, 3 and 4 months of age but this leaves them susceptible to infection in very early life, as soon as they are borne. In settings such as The Gambia, pneumococcus 'colonizes' the back of the nose (it lives there without causing disease in most cases) at very high level over these first few months.
This trial aims to find out whether giving mothers the vaccine against pneumococcus in the third trimester of pregnancy may allow them to pass protection (antibodies) to the newborn. Also whether vaccinating a baby as soon as they are born may protect them in a similar way.
If either of these approaches are successful this might provide important decision makers, such as the World Health Organisation, with new ways to prevent disease and serious infections in newborn babies.

Technical Summary

This phase 3, randomised trial will examine the role of vaccinating mothers in the third trimester of pregnancy or neonates immediately after birth with a pneumococcal conjugate vaccine (Prevenar 13™ - PCV13) in order to prevent carriage of pneumococcus in the nasopharynx between birth and 20 weeks of age.
Carriage of pneumococcus in the nasopharynx is a prerequisite for disease (pneumonia, septicaemia and meningitis) and, in the trial, prevention of carriage is a used as a surrogate for prevention of disease. The overall objective of the trial is to find new ways to combat these serious infections which occur in early life, before children are routinely vaccinated.
600 expectant mothers will be recruited in the third trimester of pregnancy and their subsequent born infants will be followed up until the age of 9 months. The mothers will be randomized either to a 'Maternal' group who will receive PCV13 in pregnancy, a 'Neonatal' group, the infants of whom will receive the vaccine at birth or a 'Control' group who's infants will receive the vaccine according to the normal schedule at 2, 3 and 4 months of age.
If the trial demonstrates either of these alternative approaches significantly reduces pneumococcal carriage in early life the potential implications in terms of modifying WHO vaccination policy are very significant.
 
Description Maternal Immunization Pharmacovigilance - Landscape Review - A Roadmap for Program Development in Low and Middle Income Countries
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact The document resulting from this advisory committee consultation is expected to be used to focus future work to measure health impacts in expectant mothers receiving vaccines in low and middle income countries as well as to direct the development of the otherwise fledgling regulatory framework globally
 
Description Participation in NIH/BMGF advisory meeting - Harmonization of Safety Reporting in Immunizations in Pregnancy
Geographic Reach Africa 
Policy Influence Type Membership of a guideline committee
Impact The meeting drove the further expansion of the use of harmonized terms for safety reporting in pregnancy
 
Description Assessment of case definitions for reporting the outcomes of maternal vaccination trials
Amount $25,000 (USD)
Organisation Bill and Melinda Gates Foundation 
Sector Charity/Non Profit
Country United States
Start 10/2017 
End 12/2018
 
Description Maternal Men A vaccination
Amount £195,000 (GBP)
Organisation Meningitis Research Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2016 
End 01/2018
 
Description Pump-priming grant - IMPRINT Network
Amount £25,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2017 
End 09/2018
 
Description Stanford University - The effects of the infant microbiome on the immune responses to vaccination
Amount $160,000 (USD)
Organisation Stanford University 
Sector Academic/University
Country United States
Start 04/2018 
End 04/2020
 
Title The development of a research platform within which to undertake maternal vaccination safety and immunogenicity trials in The Gambia 
Description Maternal vaccination trials in low income countries require the development of significant research infrastructure. IN particular we have established an antenatal ultrasound facility within which to undertake gestational ultrasound assessments (not otherwise available in the country) and a framework for the capture and reporting of safety outcomes 
Type Of Material Improvements to research infrastructure 
Provided To Others? No  
Impact The platform will be used for future research in this field in The Gambia and is also likely (based on a planned publication related to the development of the platform) to guide researchers elsewhere 
 
Description ICH London Goldblatt lab 
Organisation University College London
Department Institute of Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution scientific exchange re pneumococcal immunisation policies, practice and research, sharing of reagents and assay development
Collaborator Contribution scientific exchange re pneumococcal immunisation policies, practice and research, sharing of reagents and assay development
Impact 1 shared PhD studentship, scientific workshop at MRC The Gambia input into senior appointments
Start Year 2012
 
Description Viral illnesses in infants and mothers in the PROPEL trial 
Organisation University of Cincinnati
Country United States 
Sector Academic/University 
PI Contribution Provision of samples
Collaborator Contribution Provision of laboratory supplies and expertise
Impact Awaited
Start Year 2015
 
Title Prevenar13 (licensed vaccine) for use in expectant mothers (unlicensed indication) 
Description Prevenar13 is licensed in infants, children and adults but is not licensed in pregnancy. This trial is testing the safety and efficacy against pneumococcal nasopharyngeal carriage of the vaccine in pregnant women and newborns 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2017
Development Status Under active development/distribution
Clinical Trial? Yes
Impact The trial is currently underway and data has yet to be analysed. 
URL https://clinicaltrials.gov/ct2/show/NCT02628886