Studies to understand the response of the infant’s immune system to infectious diseases and vaccines
Lead Research Organisation:
MRC Unit, The Gambia
Abstract
Despite progress overall in reducing the number of children dying before they reach the age of five, deaths in the first year of life and even more strikingly in the first month of life have not fallen in the same way. At this age many babies die as the result of infections.
The research being carried out in the infant immunology group aims to reduce deaths from infection in this most vulnerable group though better understanding the way the immune (or defence) system works.
We want to understand the best possible ways to give some of the vaccine we already have available. This might include giving vaccine to mums so that the immunity they generate (the antibodies) can protect a baby as soon as the baby is born (before the baby can be vaccinated themselves). We also want to know how the baby’s immune system responds when it comes across an infection. If understood this better we might be able to improve these response, for example with new vaccines, so the baby would not become unwell. Finally we carry out research which gives us a better understanding of how vaccines themselves working in babies. This research includes new vaccines against malaria, HIV and TB as well as established vaccines like the pneumococcal vaccine. Understanding better the vaccines we have should allow the next generation of vaccines to be designed even more effectively so that less newborns and infants die needlessly.
The research being carried out in the infant immunology group aims to reduce deaths from infection in this most vulnerable group though better understanding the way the immune (or defence) system works.
We want to understand the best possible ways to give some of the vaccine we already have available. This might include giving vaccine to mums so that the immunity they generate (the antibodies) can protect a baby as soon as the baby is born (before the baby can be vaccinated themselves). We also want to know how the baby’s immune system responds when it comes across an infection. If understood this better we might be able to improve these response, for example with new vaccines, so the baby would not become unwell. Finally we carry out research which gives us a better understanding of how vaccines themselves working in babies. This research includes new vaccines against malaria, HIV and TB as well as established vaccines like the pneumococcal vaccine. Understanding better the vaccines we have should allow the next generation of vaccines to be designed even more effectively so that less newborns and infants die needlessly.
Technical Summary
Millennium Development Goal 4 sets out to reduce mortality in children under five-years of age. Despite progress with this overall, including in many countries across sub-Saharan Africa, mortality in infancy and in particular in newborns has so far been comparatively resistant to intervention. Although the reasons for this are multi-factorial, many deaths in this period occur as a result of infections. Consequently, understanding the distinct way in which infants respond to infections and vaccines, facilitating the rational development of novel interventions to protect newborns is a top global health priority. These areas are the focus of current research within infant immunology.
Objectives:
To characterise the key elements of the immune response to given pathogens (e.g. pneumococcus, staphylococcus) which may be associated with the development of natural immunity to these agents in order to facilitate the develop novel protective strategies
To describe, at both a cellular and a humoral level, the immunity generated by currently licensed (e.g. rotavirus) as well as experimental (e.g. malaria, HIV, TB) vaccines in order to guide future rational vaccine development
To establish the optimum regimens for the use of current vaccines (e.g. inactivated poliovirus vaccine, pneumococcal conjugate vaccines) which will maximise the protection of infants while also ensuring the logistical challenges of vaccine delivery on a large scale (e.g. through using fractional doses, novel delivery methods, maternal immunisation, multi-dose vials) are met
Methodology:
These critical objectives are being addressed across a series of maternal and infant cohorts.
A combination of interventional studies, including GCP-clinical vaccine trials, as well as longitudinal observational studies, is used according to the questions being addressed. We have the established capacity to recruit mothers antenatally allowing newborns to be followed right from delivery. We also recruit infants over the first year of life as they are presented for their routine immunisations
A range of laboratory approaches are used including large-scale serological studies monitoring correlates of vaccine induced protection, as well detailed immunological investigations. Such studies, which are often nested within larger scale trials, use techniques including multi-parameter flow-cytometry, ELISpot assays, evaluation of cytokines and antibodies using Luminex-based multi-analyte technology.
Impact
The findings of certain key studies (e.g. inactivated poliovirus vaccine trial) are expected to directly influence WHO policy over the coming year. Other work is focussed on studying pathogens (e.g. pneumococcus, malaria, rotavirus) which remain at the top of the research agenda internationally and address question recognised to be high priority.
Objectives:
To characterise the key elements of the immune response to given pathogens (e.g. pneumococcus, staphylococcus) which may be associated with the development of natural immunity to these agents in order to facilitate the develop novel protective strategies
To describe, at both a cellular and a humoral level, the immunity generated by currently licensed (e.g. rotavirus) as well as experimental (e.g. malaria, HIV, TB) vaccines in order to guide future rational vaccine development
To establish the optimum regimens for the use of current vaccines (e.g. inactivated poliovirus vaccine, pneumococcal conjugate vaccines) which will maximise the protection of infants while also ensuring the logistical challenges of vaccine delivery on a large scale (e.g. through using fractional doses, novel delivery methods, maternal immunisation, multi-dose vials) are met
Methodology:
These critical objectives are being addressed across a series of maternal and infant cohorts.
A combination of interventional studies, including GCP-clinical vaccine trials, as well as longitudinal observational studies, is used according to the questions being addressed. We have the established capacity to recruit mothers antenatally allowing newborns to be followed right from delivery. We also recruit infants over the first year of life as they are presented for their routine immunisations
A range of laboratory approaches are used including large-scale serological studies monitoring correlates of vaccine induced protection, as well detailed immunological investigations. Such studies, which are often nested within larger scale trials, use techniques including multi-parameter flow-cytometry, ELISpot assays, evaluation of cytokines and antibodies using Luminex-based multi-analyte technology.
Impact
The findings of certain key studies (e.g. inactivated poliovirus vaccine trial) are expected to directly influence WHO policy over the coming year. Other work is focussed on studying pathogens (e.g. pneumococcus, malaria, rotavirus) which remain at the top of the research agenda internationally and address question recognised to be high priority.
Organisations
- MRC Unit, The Gambia, Gambia (Lead Research Organisation)
- University College London, United Kingdom (Collaboration)
- Public Health England, Salisbury (Collaboration)
- National Institute for Public Health and Environment (RIVM) (Collaboration)
- Merck (Collaboration)
- Boston Children's Hospital (Collaboration)
- University of Cincinnati (Collaboration)
- Novartis Institutes for Biomedical Research (NIBR) (Collaboration)
Publications

Afolabi MO
(2014)
Early phase clinical trials with human immunodeficiency virus-1 and malaria vectored vaccines in The Gambia: frontline challenges in study design and implementation.
in The American journal of tropical medicine and hygiene

Ahmed N
(2020)
Potential cost-effectiveness of a maternal Group B streptococcal vaccine in The Gambia.
in Vaccine

Bamford A
(2014)
Serological response to 13-valent pneumococcal conjugate vaccine in children and adolescents with perinatally acquired HIV infection.
in AIDS (London, England)

Bashorun A
(2022)
Intradermal administration of fractional doses of the inactivated poliovirus vaccine in a campaign: a pragmatic, open-label, non-inferiority trial in The Gambia
in The Lancet Global Health

Basu Roy R
(2012)
Current understanding of the immune response to tuberculosis in children.
in Current opinion in infectious diseases

Battersby AJ
(2012)
Vitamin D in early childhood and the effect on immunity to Mycobacterium tuberculosis.
in Clinical & developmental immunology

Bittaye M
(2021)
Viewpoint: vaccine inequity in the spotlight
in Archives of Disease in Childhood

Burl S
(2011)
Age-dependent maturation of Toll-like receptor-mediated cytokine responses in Gambian infants.
in PloS one

Clarke E
(2021)
Immunogenicity and safety of a novel ten-valent pneumococcal conjugate vaccine in healthy infants in The Gambia: a phase 3, randomised, double-blind, non-inferiority trial.
in The Lancet. Infectious diseases
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 | Member - Bill & Melinda Gates Foundation Expert Advisory Group on Single Dose HPV vaccine scheduling |
Geographic Reach | Africa |
Policy Influence Type | Membership of a guideline committee |
Impact | The expert committee has been set up to drive the research and implementation agenda for single dose HPV vaccine schedules in Low and Middle Income Countries |
Description | Member - National Immunization Technical Advisory Committee - The Gambia |
Geographic Reach | National |
Policy Influence Type | Participation in a advisory committee |
Impact | The National Immunization Technical Advisory Group advised the Ministry of Health on vaccination policy decisions in The Gambia and has a direct impact on vaccination policy within the childhood immunization schedule |
Description | Novartis maternal immunisation strategy board |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in advisory committee |
Impact | the advice from the group of which I was an scientific member led to critical appraisal within industry which vaccines to push forward for maternal immunisation. |
Description | Pfizer GAVI advisory board |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in advisory committee |
Impact | possible impact, as Nigeria haas now introduced the PcV vaccine which was advised by the board |
Description | Press panel RCPCH |
Geographic Reach | National |
Policy Influence Type | Participation in a national consultation |
Description | WHO Polio Research Committee Meeting attendance and data presentation |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a advisory committee |
Impact | Based on funded research undertaken at the Unit we presented data to the WHO polio research committee on delivery of fraction doses of IPV in outbreak campaigns. Such data has the potential to directly impact WHO policy recommendations regarding polio outbreak control. |
Description | WHO advisory board |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in advisory committee |
Impact | improvements in delivery of clinical services to children exposed to TB by advocating contact tracing for vulnerable groups in the WHO guideline document to which I contributed |
Description | introduction of new vaccine in The Gambia EPI |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Implementation circular/rapid advice/letter to e.g. Ministry of Health |
Impact | In August 2013 the Government of The Gambia introduced the Rotavirus vaccine into the EPI schedule. This was amongst other things prompted by data from the MRC Unit showing that rotavirus made a significant contribution to morbidity and mortality in children in The Gambia. The lab work was led by Vaccinology (Dr Antonio) |
Description | Al Thrasher Award |
Amount | $350,000 (USD) |
Organisation | Thrasher Research Fund |
Sector | Charity/Non Profit |
Country | United States |
Start | 11/2014 |
End | 11/2017 |
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 | 09/2017 |
End | 12/2018 |
Description | Clinical Trial scheme MRC/DFID/WT |
Amount | £1,300,000 (GBP) |
Organisation | Government of the UK |
Department | Department for International Development (DfID) |
Sector | Public |
Country | United Kingdom |
Start | 01/2015 |
End | 01/2018 |
Description | Global Health Wellcome Trust fellowship Dr LeDoare |
Amount | £55,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2013 |
End | 09/2014 |
Description | Investigator initiated proposal |
Amount | $350,000 (USD) |
Organisation | Pfizer Ltd |
Sector | Private |
Country | United Kingdom |
Start | 03/2012 |
End | 03/2014 |
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 | N/A |
Amount | $4,700,000 (USD) |
Organisation | PATH Vaccine Solutions |
Sector | Charity/Non Profit |
Country | United States |
Start | 12/2016 |
End | 09/2018 |
Description | PCV10 Clinical Vaccine Trial Scheme |
Amount | $1,900,000 (USD) |
Organisation | PATH |
Sector | Charity/Non Profit |
Country | Global |
Start | 08/2013 |
End | 07/2016 |
Description | PhD studentship Dr Battersby |
Amount | £370,000 (GBP) |
Funding ID | 098980/Z/12/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2013 |
End | 02/2016 |
Description | Project grant Polio trial BMGF |
Amount | $2,000,000 (USD) |
Organisation | Bill and Melinda Gates Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 01/2013 |
End | 07/2016 |
Description | Pump-priming grant - IMPRINT Network |
Amount | £25,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2017 |
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 | 03/2018 |
End | 04/2020 |
Description | Wellcome Trust Training Fellowship |
Amount | £247,000 (GBP) |
Organisation | Wellcome Trust |
Department | Wellcome Trust Research Training Fellowship |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2014 |
End | 09/2017 |
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 | Harvard Levy lab |
Organisation | Boston Children's Hospital |
Country | United States |
Sector | Hospitals |
PI Contribution | exchange of staff and technology |
Collaborator Contribution | contributed research samples |
Impact | publication by Burl et al |
Start Year | 2010 |
Description | Harvard Levy lab |
Organisation | University College London |
Department | Institute of Child Health |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | exchange of staff and technology |
Collaborator Contribution | contributed research samples |
Impact | publication by Burl et al |
Start Year | 2010 |
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 | Merck Vaccines |
Organisation | Merck |
Country | Germany |
Sector | Private |
PI Contribution | As part of a clinical trial of HPV vaccines we will provide serum samples to Merck to analyse on their multiplex based serology platform which has been used in past efficacy trial of the vaccine. The results will be provided to us (MRC Unit The Gambia) for analysis. |
Collaborator Contribution | As part of a clinical trial of HPV vaccines we will provide serum samples to Merck to analyse on their multiplex based serology platform which has been used in past efficacy trial of the vaccine. The results will be provided to us (MRC Unit The Gambia) for analysis. |
Impact | Nil as yet - trial underway |
Start Year | 2016 |
Description | Novartis Vaccine development |
Organisation | Novartis Institutes for BioMedical Research (NIBR) |
Department | Novartis Vaccines Institute for Global Health (NVGH) |
Country | United States |
Sector | Private |
PI Contribution | generated data for pertussis seroprevalence |
Collaborator Contribution | funding for consumables |
Impact | manuscript in progress |
Start Year | 2011 |
Description | Public Health Engalnd |
Organisation | Public Health England |
Country | United Kingdom |
Sector | Public |
PI Contribution | Provision of clinical trial serum samples |
Collaborator Contribution | Processing of clinical trial serum samples for serological analysis |
Impact | Presentation of clinical trial results and World Health Organisation Meeting |
Start Year | 2012 |
Description | RIVM Holland |
Organisation | National Institute for Public Health and Environment (RIVM) |
Department | Centre for Infectious Diseases, Epidemiology and Surveillance |
Country | Netherlands |
Sector | Public |
PI Contribution | analysis of samples at MRC using RIVM technology, following successful tec transfer from RIVM results on pertussis of interest to RIVM epidemiologists |
Collaborator Contribution | facilitating Tec Transfer to MRC by hosting 2 technicians |
Impact | 1 manuscript submitted, 1 in preparation |
Start Year | 2011 |
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 | 10 valent pneumococcal conjugate vaccine manufactured by the Serum Institute of India (generic for GAVI purchase) |
Description | We have recently completed a phase 1/2 trial and a phase 3 licensure trial is now planned |
Type | Therapeutic Intervention - Vaccines |
Current Stage Of Development | Early clinical assessment |
Year Development Stage Completed | 2017 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | The phase 1/2 trial completed and the phase 3 trial planned aim to result in the licensure of the first generic pneumococcal conjugate vaccine specifically targeting those pneumococcal serotypes prevalent in low and middle income countries |
URL | https://clinicaltrials.gov/ct2/show/NCT02308540?term=VAC017&rank=1 |
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 |
Title | polio needleless devices |
Description | 2 needleless devices to administer vaccines are currently under evaluation within Vaccinology/Inf Immunology. funding: BMGF/PATH |
Type | Therapeutic Intervention - Medical Devices |
Current Stage Of Development | Late clinical evaluation |
Year Development Stage Completed | 2013 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | trial ongoing |
URL | http://clinicaltrials.gov/show/NCT01847872 |
Title | polio vaccine |
Description | currently conducting new application of polio vaccine to be given i.m at 9 months with other EPI vaccines funding: BMGF |
Type | Therapeutic Intervention - Vaccines |
Current Stage Of Development | Refinement. Clinical |
Year Development Stage Completed | 2013 |
Development Status | Under active development/distribution |
Clinical Trial? | Yes |
Impact | trial in progress |
URL | http://clinicaltrials.gov/show/NCT01847872 |
Description | Community sensitisation events |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Participants in your research and patient groups |
Results and Impact | The community sensitisation events are regularly conducted to inform past, present and future participants in our research on the results of previous studies and upcoming new research studies and clinical trials. They serve as a link to the community decision makers and are well supported by community members and MRC researchers. Increased participation in clincial trials and ongoign research |
Year(s) Of Engagement Activity | 2010,2011,2012,2013,2014 |
Description | Inaugural lecture |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Travel with T cells, now on YouTube inerest in academic medicine by GCSE-level students, several University students requesting mentorship |
Year(s) Of Engagement Activity | 2012 |
Description | MRC Unit The Gambia - Scientific Open Day |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Open day for schools. study participants, influential community members and members of government to increase understanding of MRCG at LSHTM research |
Year(s) Of Engagement Activity | 2013,2014,2015,2016,2017,2018,2019 |