IMPRINT Projects

The following projects have been selected for funding through IMPRINT:

Challenge 1: Mechanism of production and transfer of maternal antibody via the placenta and breast milk

Summary

Young infants are more susceptible to infection than individuals at any other life stage. Their immune systems are inexperienced and they are too young to benefit from infant vaccination, most of which are given several weeks after birth. In the first weeks of life, babies rely on protective proteins called antibodies, which are transferred across the placenta from the mother to the baby whilst still in the womb. In some cases, the amount of antibody transferred to the baby is not sufficient to protect the baby from infections, such as whooping cough. Vaccines given in pregnancy aim to increase the amount of antibody in the mother’s blood, so that more antibody is transferred across the placenta to the baby so that the infant is protected until they are old enough to receive infant vaccines.

Antibody is transferred across the placenta by binding to specialised receptors on the surface of placental cells. In this project, we aim to study each part of the antibody-receptor interaction, namely:

  • Functional changes in the antibody
  • The amount and location of the antibody receptor
  • The strength of the binding between the antibody and the receptor

We aim to understand how these factors change throughout pregnancy, by testing stored blood and placental samples. We will also look at how vaccination in pregnancy can affect these factors.

In developing countries, a significant proportion of pregnant women are affected by HIV infection. This can affect how well antibody is transferred across the placenta. We aim to understand how HIV affects the maternal antibody and how well it binds to the receptor in the placenta.

We hope that this project will help us understand more about the way babies are protected by vaccines in pregnancy and in the future, help us design vaccines that are more effective at protecting the mother and infant.

Project lead

Dr Chrissie Jones
Associate Professor and Honorary Consultant in Paediatric Infectious Diseases Clinical and Experimental Sciences
Room LF102, F Level
South Academic Block University Hospital Southampton NHS Foundation
Trust Tremona Road
Southampton SO16 6YD
United Kingdom

IMPRINT partner

Beth Holder, Imperial College London, London, UK

Project duration

12 months

Summary

Pregnant women sometimes carry a bacterium called Group B Streptococcus (GBS) in their vagina or rectum. During pregnancy or upon delivery, GBS may be transmitted to the baby resulting in the death of the baby in the womb or go on to cause infections such as sepsis or meningitis soon after birth. GBS disease is more serious in some low- and middle-income countries (LMICs) where pregnant women do not have access to proper antenatal care and antibiotics. A solution would be to vaccinate mothers against GBS, so they can produce antibodies protective proteins (antibodies) that can be transferred to the baby through the placenta and protect them from developing an infection in the first place. Interestingly, LMICs situated in South-East Asia report a low GBS disease burden while high GBS disease rates are documented on the African continent, in countries such as Malawi or South Africa.

In this project we aim to collect the blood of GBS-colonised mothers from high vs. low GBS disease burden countries (U.K. vs. Malawi vs. Bangladesh) and compare how the immune system of the women reacts to GBS by measuring anti-GBS antibody concentrations, the ability of the antibody to kill the bacteria, as well its ability to bind to factors present on the surface of the GBS bacteria. We also aim to examine how effectively the antibodies are transferred across the placenta and give protection to babies.

By comparing the properties of antibodies collected from high- vs low- disease burden countries, we hope to understand the criteria that are essential for the optimal transfer of GBS protective antibodies from mother to baby. Altogether this knowledge will significantly help towards the design of more efficient and safe vaccines to protect new born babies from life-threatening GBS disease.

Project lead

Dr. Shadia Khandaker
Department of Clinical Infection, Microbiology and Immunology
Institute of Infection and Global Health
University of Liverpool
United Kingdom

IMPRINT partner

Prof. Aras Kadioglu, University of Liverpool, United Kingdom
Prof. Neil French, University of Liverpool, United Kingdom
Prof. Samir Kumar Saha, Child Health Research Foundation (CHRF) Bangladesh Institute of Child Health Research Foundation, Dhaka Shishu (Child) Hospital, Bangladesh

Project duration

24 months

Shadia Khandaker

Shadia Khandaker

Shadia is a Clinical Microbiologist who possess an intrinsic aspiration for research in paediatric infectious disease and its prophylactic management. She is currently finishing her PhD thesis as a Commonwealth Scholar in the Institute of Infection and Global Health at the University of Liverpool. She holds a M. Phil in Microbiology as well as a Bachelor in Medicine and Surgery.

From 2012 on she has been serving as an Assistant Professor at the Department of Microbiology, Ibrahim Medical College, Bangladesh and will return to her position after completing her postdoctoral research. Her career history entails a variety of positions including academic, laboratory consultant, teacher and researcher in the field of medical microbiology.

Challenge 2: Effects of maternal immunisation on the subsequent development of immunity in the infant

Summary

Whooping cough can cause serious disease, particularly in young infants. In the UK, and other countries around the world, it is recommended that pregnant women receive the whooping cough vaccine in order to protect mothers and infants against whooping cough. Antibodies (protective proteins) are transferred across the placenta from the mother to the infant and protect the infant in the first months of life, before the infant is protected by infant whooping cough vaccination. There are concerns that high levels of maternal antibody in the infant at birth may prevent the infant from producing such a good response to their own vaccines.

There is a type of blood cell in the circulation called “T Follicular Helper” cells (or TFH cells for short.) These cells are thought to be important for how well the body produces the protective antibody proteins in response to vaccination. It is important to understand if vaccination in pregnancy can affect how well these specialised cells develop in the infant’s blood stream and therefore how well the infant responds to their own vaccines. Other specialised cells that are important to how well the infant responds to infections like whooping cough, such as “T” cells, may also potentially be affected by vaccination in pregnancy.

In this study, we will work with partners in Thailand who are already carrying out studies looking at whooping cough vaccination in pregnancy. We will work with samples that have already been collected, from infants born to vaccinated mothers and infants born to unvaccinated mothers. This will allow us to compare the infant’s cellular response to vaccination in these different groups of infants.

We hope that this study will improve our understanding of infant immunity and inform future vaccination strategies.

Project lead

Dr Qibo Zhang
Senior Lecturer in Immunology
Institute of Infection and Global Health
University of Liverpool
Southampton, United Kingdom

IMPRINT partners

Dr Elke Leuridan, University of Antwerp, Belgium
Prof. Yong Poovorawan, Chulalongkorn University, Thailand

Project duration

12 months

Summary

The ultimate aim of our work is to develop vaccines that will be taken by pregnant women and which will then protect babies from catching infections caused by, for example, HIV, hepatitis B and Zika, during birth. The vaccines will be taken by mouth, but will have their effects in the mother’s vagina. The oral route of vaccine taking has been chosen as this route is expected to have higher acceptability and be cheaper than injections, which have to be sterile, need to be given by medically-trained personnel and can be painful. The cost factor is especially relevant in LMIC, for poorer people and where healthcare costs are largely borne by individuals, rather than the state.

For oral vaccines to have an influence in the vagina, they have to be prepared using specific chemicals, such that once a vaccine is swallowed, it is only processed in the large bowel (and nowhere else in the gut). In this project, we will: i) identify those chemicals, ii) prepare the vaccines, and iii) test whether the prepared vaccines will be processed in the large bowel following swallowing.

The results of this study will be used to apply for follow-on funding to determine whether such vaccines will have an influence in the mother’s vagina and protect newborns during birth.

Project lead

Dr Sudaxshina Murdan
Reader in Pharmaceutics
UCL School of Pharmacy
University College London
London, United Kingdom

IMPRINT partners

Prof. Abdul Basit, University College London, United Kingdom
Dr Fatme Mawas, National Institute for Biological Standards and Control, MHRA, United Kingdom

Project duration

8 months

Summary

Whether vaccines given to women in pregnancy (maternal immunization) have an effect on the developing immune system of the newborn baby are still not well understood. However, this knowledge is important to make sure that current and future vaccines used in pregnancy can be used in the most efficient and protective way. Whilst we have better insights into the effect of the maternal vaccines on the antigen-specific, acquired immune responses in the newborn, but there remains a gap in knowledge about effects of maternal vaccination on infant natural defense cells (innate immunity) and any potential modification of these cells.

This project will use cord blood samples collected within an ongoing large-scale observational study of neonatal vaccine responses to develop a prototype of assays in the lab that will allow us to investigate the effects of maternal antibody on the natural defense cells in the newborn. Initially we will use the model of tetanus vaccination, given that this vaccine is already routinely given to pregnant women in The Gambia. This model can then serve to assess the potential impact of other maternal vaccines on neonatal innate responses, such as pertussis or future vaccines. In addition, we will examine in another lab assay whether "training" of specific cells generated from cord blood (monocytes) by BCG -another vaccine used in the newborn- can induce changes in gene expression. We will also have the opportunity to measure if the early natural cellular responses have an influence on the antibody levels measured in response to vaccines the baby receives in the first few months of life.

This knowledge will help us to estimate if there is potential for clinical impact on longer term antigen-specific immunity in the infants or not.

The fellowship is embedded in an existing strong research partnership between the three research sponsors in Gambia, Vancouver and Brussels and will provide the fellow with the opportunity to develop an independent complimentary aspect of the research around one of the key challenges identified by the IMPRINT network.

Project lead

Dr Alansana Darboe
Vaccine & Immunity Theme
Medical Research Council Unit The Gambia at the London School of Hygiene and Tropical Medicine

IMPRINT partners

Prof. Beate Kampmann, Imperial College London, United Kingdom
Prof. Tobias Kollmann, University of British Columbia, Canada
Prof. Arnaud Marchant, Université Libre de Bruxelles, Belgium

Project duration

24 months

Dr Alansana Darboe

Dr Alansana Darboe

Alansana received his BSc. (Hons) Biomedical Science in 2010 from the University of Manchester and his Doctorate of Philosophy in 2017 from the University of London, at the London School of Hygiene & Tropical Medicine. His career at the MRC Unit the Gambia at the London School of Hygiene & Tropical Medicine started in 2003 where he, among other positions held, served as High Scientific Officer from 2012-2016. Since 2017 he holds a postdoc position at MRC with a strong focus on Systems Biology to Identify Biomarkers of Neonatal Vaccine Immunogenicity and breakthrough infections of hepatitis B virus after vaccination. His IMPRINT funded 2 years fellowship project will tie up with his existing projects and scientific knowledge.

Challenge 3: Impact of globally important co-factors on maternal and neonatal immunity

No project selected yet – applications in current and/or upcoming calls are highly welcome!

Challenge 4: Vaccine acceptancy and preparedness for maternal immunisation, including in emergencies

Summary

Giving vaccines to pregnant women is a useful public health measure. It will help to reduce death and disease among pregnant women and newborn infants from infectious diseases. This will be most important in low- and middle-income countries (LMIC). New vaccines are being developed for use in pregnant women e.g. for Group B streptococcus, respiratory syncytial virus and cytomegalovirus. The safety of vaccines administered to pregnant women is most important for pregnant women, healthcare providers, researchers, regulators, ethics committees, vaccine developers and communities. There is a need for a global coordinated approach to determine the safety of vaccines used for pregnant women and for Maternal and Child Health (MCH) studies. The GAIA (Global Alignment of Immunization safety Assessment in pregnancy) project has developed 21 globally consistent tools (case definitions of key terms) to determine the safety of vaccines in pregnancy. These can also be used for MCH studies. Assessment of these tools in LMIC is required. This study will assess key case definitions and terms using data from clinical studies conducted in South Africa and The Gambia. The study will determine how possible it is to utilize the case definitions, the quality and accuracy of the data collected, the challenges and advantages of using the case definitions and collection of any possible edits to the case definitions that would make them easy to use in LMIC.

Project lead

Sonali Kochhar, MD
Medical Director,
Global Healthcare Consulting
Scientific Researcher,
Department of Public Health
Erasmus University Medical Center
Rotterdam, The Netherlands

IMPRINT partners

Clare Cutland, University of the Witwatersrand, South Africa
Ed Clarke, MRC Unit The Gambia, Banjul, The Gambia

Project duration

9 months

Challenge 5: Vaccine safety monitoring in LMIC

No project selected yet – applications in current and/or upcoming calls are highly welcome!

Challenge 6: Development of comparable methodologies for assessing efficacy in clinical trials

Summary

Tuberculosis (TB) is a disease caused by a germ that can affect the lungs and in severe cases, the blood and the brain. Almost one million children, mostly from the tropics, suffered from TB in the year 2015. A vaccine called BCG is used to prevent this disease. It is given to babies and is able to prevent severe forms of TB that involve the blood and the brain but does not provide adequate protection from the lung form which is the most common. New vaccines that are able to do a better job at preventing TB in babies are needed. VPM1002 is a vaccine that has been developed to work better than BCG. It has been tested in adults and babies and the results show that it is safe, however we need to know how well it is able to kill TB germs. This study aims to use a tool in the lab to show how well the new vaccine, VPM1002 works in babies from Uganda, an African country where TB is common.

Project lead

Mr Simon Gwapa Kimuda
Associate Scientist
Immunomodulation and Vaccines
Medical Research Council/UVRI Uganda Research Unit on AIDS
Entebbe, Uganda

IMPRINT partners

Prof. Alison Elliott, Medical Research Council/UVRI Uganda Research Unit on AIDS, Uganda
Prof. Gerhard Walzl, Stellenbosch University, South Africa
Dr Helen Fletcher, London School of Hygiene & Tropical Medicine, United Kingdom

Project duration

12 months