IMPRINT: IMmunising PRegnant women and INfants neTwork

Far too many newborns continue to die in early life, particularly in low-and middle income countries (LMIC). Many die from infections, some of which could be prevented. During the late stages of pregnancy, antibody is transferred across the placenta from mother to child, providing protection to the infant in the early weeks of life. However, if the mother has insufficient protection against certain infections, the infant will also not be protected.

Vaccinating women in pregnancy can enhance the level of antibody in the mother, thereby protecting the mother, and increasing the amount of antibody transferred across the placenta - protecting the infant from birth too. This concept has already been successfully established for the prevention of tetanus, influenza and pertussis (whooping cough). Many investigators and stakeholders are interested in using this strategy to protect infants from other serious infections, for example group B streptococcus or respiratory syncytial virus (RSV), and vaccines against these infections are in development. Some fundamental gaps in our understanding remain about the immune response to vaccines in pregnancy and in newborn infants which are essential for us to address in order to accelerate development of new vaccines. It is also very important that the scientific community tackles how best to implement such vaccine programmes in both high-income countries and LMIC.

Our unique inter-disciplinary network represents stakeholders from basic science, immunology, vaccinology, social sciences, industry, public health and national and international policy makers who have come together in order to tackle the key challenges in the best use of vaccines in pregnancy and in newborns, and in the long term, improve maternal and newborn health.

Specifically, the IMPRINT network will implement collaborative research projects to answer fundamental biological questions about antibody transfer of antibody across the placenta, how to induce the "best" antibody, and its effect on the maturing newborn immune system. We will investigate if maternal vaccines interfere with the way in which the baby responds to vaccines later in infancy and childhood, to ensure that protection is not compromised at any stage. Co-factors such as nutrition or other infections might also change the way in which mothers and infants are protected by vaccines. Hence we need to take them into consideration if we are to ensure optimal protection of vaccines in pregnancy and early life. We will also find out why women decide to receive or not to accept vaccines in different countries in order to optimise the uptake of current and new vaccines. We will endeavour to work out how vaccine safety and effectiveness can be best monitored, given the different health care systems in different countries. Addressing these implementation challenges will enable us to better understand the issues and site-preparedness in the many geographical areas and populations in which IMPRINT investigators work.

IMPRINT is a multi-disciplinary network linking investigators in Europe, Africa and Asia and can therefore address these questions comprehensively. We are uniquely set up to investigate these challenges through the diversity of expertise, availability of samples and datasets already available through our collaboration, which the members are happy to share. Through our network, we will train researchers in LMIC to take forward these important questions, and we will be the forum to provide the best evidence for the safe and efficient use of vaccines in pregnancy and newborns for the ultimate goal of lowering maternal and newborn deaths from infections.

To improve maternal and neonatal health remains a focus of international investment in global health, given that Millennium Goals 4 and 5 were not achieved. 40% of all mortality in children under the age of 5 now falls into the neonatal period, with significant impact on economic development and welfare of the populations affected, primarily in LMIC. Infections are a major contributor to this burden.
There is increasing momentum to develop and implement maternal vaccines to prevent infections, in particular in LMIC, where the bulk of neonatal deaths continue to occur. In addition to its impact on the neonate, maternal vaccination offers the potential to improve maternal health and reduce stillbirths and prematurity, significant and under-appreciated problems in LMIC.
Our inter-disciplinary network will bring together national and international stakeholders representing basic science, vaccinology, social sciences, industry, public health and national and international policy makers around the opportunity of improving maternal and neonatal health by vaccination in pregnancy and the neonatal period. The applicants for the IMPRINT network have an established focus on LMIC and strong links with ODA-qualifying sites through collaborative sites in West (Gambia, Senegal, Sierra Leone), East (Malawi, Uganda) and South Africa, as well as Asia (India, China, Vietnam), providing the global context for this network.

The vision of IMPRINT is the widespread implementation and uptake of safe and effective pregnancy and neonatal vaccination programmes that lead to improved long-term neonatal and maternal health, in all relevant settings.

The potential academic benefits of IMPRINT are in the advancement of our understanding of the critical aspects of immunity in pregnancy and early infancy. Our focus is on the mechanisms of protection of maternal immunization and its impact on neonatal immune ontogeny, however our work is also of relevance to other maternal and neonatal infections, for which vaccines have not yet been developed. Achievement of the IMPRINT objectives concerning acceptability, safety and effectiveness of vaccination will facilitate our understanding of how to successfully implement vaccination programmes in all settings. Maintaining the trust of both vaccinators and the general public in a range of settings requires that clear and appropriate messages are conveyed to them, including that vaccine safety is being assessed robustly and proactively. There is clear academic benefit from this work to infant and childhood vaccination in general and also to other health interventions that may be required in pregnancy. These academic benefits extend to the ongoing work of all members of the IMPRINT network, some of which currently collaborate, but many of which currently do not. This is particularly so for members in LMICs and we aim within our pilot projects and fellowships to identify, support and train candidates who will then continue to develop and work in this field and bring added future value.

Achievement of our objectives would have potential economic benefits from the prevention of infection-related deaths and disabilities in neonates, young infants and their mothers. As the bulk of global neonatal deaths and disabilities occur in LMICs the widespread implementation and uptake of effective pregnancy and neonatal vaccination programmes will be most evident in these settings. For certain candidate vaccines, such as group B streptococcus, the potential benefits extend to the young infant, the mother and with the additional benefit of reducing stillbirths and prematurity, significant and under-appreciated problems in LMIC.

The potential societal benefits anticipated include the improvement in child and family health and quality of life through avoidance of the disruption and disabilities that result from maternal and neonatal infections. These often result in additional burdens (including loss of income) for families in caring for affected patients and prevents them from receiving adequate education and ultimately reduces their contributions to society. Additionally, the lessons learned can be transferred for the benefit of other initiatives in pregnant women and young infants such as improving the uptake of other antenatal initiatives and of routine vaccinations, with resultant societal benefits.