London School of Hygiene & Tropical Medicine

You are the Director of the IMmunising PRegnant Women and INfants neTwork (IMPRINT). What is IMPRINT?

The IMPRINT Network is a vaccine research network that addresses biological and implementation challenges associated with the use of vaccines in pregnant women and young infants. The programme of work has been ongoing for the last seven years and we now have over 380 members from 51 countries, including pediatricians, midwifes, social scientists, statisticians, stakeholders from public health and clinical trials, it’s a whole ecosystem.

Of the five vaccine networks funded by UKRI in 2017, we're the only network that focuses on maternal and newborn vaccines in order to prevent infectious diseases that can affect either the pregnant women, their babies or both. The work is carried out in high- and low- income countries.

Can you tell us a little more about what IMPRINT does?

About 50% of deaths under the age of five occur within the neonatal period, that is the first four weeks of a child’s life. As a paediatrician, I've always asked myself, is there more we can do rather than looking after already sick neonates?

Maternal vaccination capitalises on the ‘gift of nature’ that protects newborn babies in the first few months of life. That is maternal antibody, which passes form the mother to the fetus in later stages of pregnancy. The principle is well established with various vaccines, tetanus, whooping cough and influenza, where giving the vaccine to the mother in pregnancy raises specific antibodies. When these are transmitted via the placenta, these then protect the baby against specific infections that could cause serious harm, particularly in the neonatal period.

As with all vaccines but particularly with use in pregnancy, safety is absolutely paramount. You need to not only look after the pregnant woman, but you're also looking after the pregnancy outcome, you're looking after any impact around the time of delivery, and then you're also looking after the baby afterwards. So you have a responsibility to include all of these aspects.

There are also some gaps in knowledge still, as we don't know all about placental antibody transfer, and we don't know all about how the maternal antibody might or might not interfere with vaccine responses of the baby afterwards.

And then there's a huge implementation challenge, because vaccines usually sit on the expanded program of immunisation (EPI) platforms and they don't have much to do with antenatal clinics. Hence, if you are giving vaccines in pregnancy, you want to make sure that the mother and the baby are seen as a unit and we can link our observations and data between the time vaccines were delivered as well as the outcome data, for that we need to create a continuum.

So the IMPRINT network brings together people who are working all along this chain from biological challenges through to implementation, to build understanding at all of these levels, achieve equity in access and opportunities for vaccination for pregnant women.

What are the current gaps in maternal and infant vaccine coverage and what needs to be done to address some of these current gaps?

We currently don’t have vaccines for all the diseases that we're concerned about. We can protect against tetanus, whooping cough and influenza and, more lately, we can also protect potentially against RSV, a respiratory virus which is a massively important infectious disease in neonates. But we still don't have a vaccine against Group B strep, which is also a very important cause of disease and deaths in newborn babies.

The vaccines we eventually want to administer have to be needs led. Is this a disease that has a particular bad outcome in pregnancy? In which case the vaccine protects primarily the mother. Does it have a particularly bad outcome in infants? In which case you focus on pathogens affecting infants.

So, in summary, in the IMPRINT network, stakeholders work towards the design of these vaccines, safety, clinical trials, and ultimately, the regulatory side of things and implementation. We need to consider the perception of risk in the people who receive the vaccine and put in place a reliable supply of a safe and effective product which has been tested in pregnant women, so that there's certainty that it will have a beneficial impact. 

The IMPRINT website has a number of freely available animations and tools that can be used by pregnant women, healthcare professionals and anyone interested.

Alongside IMPRINT you are also the chief investigator on the  “Get Ready, Get Real” project, can you tell us more about what that project is doing?

The Get Ready, Get Real project envisions advancing the safe introduction of vaccines for pregnant women globally and will collect critical background information on pregnancy and infant outcomes over 18 months. The project has been an evolution of my thinking around not only the product, but the implementation of the product, and the way that we can assess its safety and efficacy.

Get Ready, Get Real is trying to, at least for the countries involved and for the sites involved, set a standard of data collection. The project goes beyond clinical trials and has been collecting data from public health run clinics in four countries in Africa and two countries in Asia. They’ve collected real-life data over the past three years on how many women are actually attending antenatal clinics, at what gestational age as well as on the outcome of the pregnancies, and any adverse events of special interest.

In addition to this, one thing I noted very quickly when I was doing vaccine trials enrolling pregnant women, as well as in most health systems, is that the mothers and their infants are treated as separate entities. Yet safety and outcome questions can only really be answered with confidence if you have a continuum of care and documentation.

Get Ready, Get Real is therefore also developing tools for pregnancy registries, as a way to, preferably electronically, link the outcome of a mother to her history of vaccination and the outcome of a baby to the maternal history of vaccination. There have to be bespoke solutions and the Get Ready, Get Real project is trying to work with the sites to develop such bespoke solutions, as one science rarely fits all.

Can you comment on the importance of working with governments and engaging policy-makers in vaccine research?

Most countries accept the value of vaccines for their societies, vaccines have saved more lives than any other intervention, apart from clean water. However, it's not good enough to just have a vaccine, you need to have a vaccine that's actually administered. In order to make it used, you need to engage with the people who have to deliver it, and the programmes that deliver it are run by governments.

Governments have to assess cost effectiveness, and they have to assess the value for their particular setting. That's why it's really important to not just think about your clinical trial but you have to think about how is this product going to be implemented later on? Do they even want to have the product?

We saw it with the COVID-19 vaccines, we gave out COVID vaccines in The Gambia and they asked why have you not brought us a malaria vaccine? It would be much better, that's really what we need.

So you need to test out your intervention with the people in the places where you think it's needed and ideally, the need should be driven from the ground. That's why it's absolutely important to engage with governments and think through the ecosystem involved.

This year is the 50^th anniversary of the Expanded Programme on Immunisation (EPI). Can you comment on the impact of vaccine programmes such as EPI and their future?

EPI is an infrastructure that was, I think, one of the most successful programmes the WHO ever set up, and we should celebrate it on a daily basis, and World Immunisation week at least reminds us once a year.

What's really interesting is that when the EPI system was set up, people were primarily thinking about vaccinating children. Because of the success of the children's vaccination programmes and the millions of deaths that have been prevented, it has been perceived that vaccines are not just for children, but they can also save lives in later life. The HPV vaccine is a very good example of that. So the 2030 WHO vaccine agenda emphasises that vaccines are for life and not just for children.

EPI is a framework that has not only been very successful, but has also set a precedent for how particular health interventions can be funded internationally, especially in low- income settings. The Gavi support and the commitment of high- income countries to supporting vaccination in low- income countries has been an important backbone to the EPI system.

It's great that the EPI program is now 50 years old, but the job is not done because there are many children and adults who should be getting lifesaving vaccines and yet, they are missing out. Primarily this is due to supply chain, logistics and socioeconomic reasons, all of which can be addressed. That is why it's really important to keep the issue of vaccines on people's radar, and I think the annual World Immunisation week helps to remind us of the value of vaccines.

Why do you think World Immunisation Week is important?

It's a really important opportunity to draw attention to a topic that affects us all and highlight the importance of vaccination throughout the life course.

We've just had a massive measles problem in the UK, which is an entirely vaccine-preventable disease. Yet, because until recently we hardly saw measles in the UK, and because of a degree of vaccine fatigue following COVID, measles vaccine coverage has decreased to a dangerous level, But, as we have just seen, diseases like measles are not going away and if we do not pay attention on a regular basis to the need for vaccines, then we will have outbreaks, be it in high- or low- income countries.

World Immunisation Week is also a good opportunity to give some thought to the latest developments regarding vaccine manufacturing that's coming out of countries in Africa. Because of the experience with the COVID vaccines and shortage of supplies for lower income countries, there is now a significant drive towards its own vaccine production in Africa.

We need to think about the connections and implications of the plan for action of vaccine manufacturing in Africa for global vaccine supplies, EPI programs and capacity building around vaccine, so that countries who have to date primarily relied on delivery of vaccines from abroad can also contribute to global vaccine supplies, and not just in emergencies.