An international team of researchers has pioneered a technique which gives unprecedented insight into the dramatic changes occurring in a baby’s body in the first week of life – all using less than a quarter of a teaspoon of blood.
A research consortium including scientists from the Wesfarmers Centre of Vaccines & Infectious Diseases, based at The Kids Research Institute Australia, was able to chart thousands of processes kicked off at the time of birth, including almost 2,000 genes being turned on and off, the making of proteins, and the establishment of metabolic pathways.
The study, published today in Nature Communications, gives researchers a baseline for health and disease in early life that can help measure responses to key medical interventions such as vaccines, as well as the impact of factors such as diet, disease and maternal health.
The study was conducted by the Expanded Program on Immunization Consortium (EPIC), a collaboration spearheaded by world-leading infectious disease experts Professor Ofer Levy, director of the Precision Vaccines Program at Boston Children’s Hospital, Professor Beate Kampmann from the London School of Hygiene and Tropical Medicine, and Professor Tobias Kollmann, of the University of British Columbia. Professor Kollmann will relocate from Canada to Perth next month, where he will head The Kids’ Personalised Medicine Centre for Children and lead the Institute’s involvement in the international Human Vaccines Project.
The Kids’ role in the EPIC study, which included recruiting and obtaining samples from one of two groups of newborns used for the investigation, was led by Dr Anita Van Den Biggelaar, University of Western Australia and Wesfarmers Centre Professor Peter Richmond, and Professor William Pomat – Director of the Papua New Guinea Institute of Medical Research and an honorary research fellow at The Kids.
Professor Richmond said EPIC arose out of a desire to understand more about how newborn babies’ immune systems develop, and how they respond to vaccinations.
“In the past we haven’t had the tools to look in depth at the immune response in very early life, because the necessary testing required large volumes of blood which can’t be taken when babies are that small,” Professor Richmond said.
“What previous work has been done used blood taken from the baby’s umbilical cord after birth, because it was easier to obtain the volume needed – however what we’ve found is that when you measure what’s happening in the baby itself rather than the cord blood, it’s quite different.”
The researchers instead took a systems biology approach, developing tests that could be carried out on less than a quarter of a teaspoon of newborn blood. Systems biology uses computer and mathematical models to understand complex biological systems.
“As a result we’ve gone from the 4-5 tablespoons of blood that might be needed for standard testing, to less than 1ml,” Professor Richmond said.
“By being very careful in the way we collect and process these specimens, we’ve been able to obtain and analyse a huge amount of data. We’re using the latest in technology, but miniaturising it so it can be used in newborn babies.”
Using these new tests, the researchers were able to identify a series of dramatic changes that added up to a remarkably stable and purposeful, rather than random, developmental trajectory over the first week of life. This included more than 1860 genes being turned on and off, and more than 350 different metabolic pathways and chemical changes.
“It’s much more complex than you would have thought,” Professor Richmond said. “It’s quite clear that even in these first few days babies are setting down a roadmap for immune development, the colonisation of their microbiome, and countless other processes which will help determine the direction they’re going in for the rest of their life.”
He said although the researchers intended to use the breakthrough to optimise the design of vaccines so babies could be protected more quickly and with longer lasting immunity, the information obtained from the tiny samples of blood would help deepen the understanding of newborn health more broadly.
“Being born is one of the most dangerous things that ever happen, and it’s a time when babies, particularly in developing countries, can be highly susceptible to infections – which is why we’re so interested in understanding the baby’s immune response and the impact of vaccines at this critical time,” Professor Richmond said.
“However, the enormous amount of information we’ve been able to obtain through this approach has application to many other fields focused on the start of life and what we can do to improve it.
“The significance of this big data approach is that we will find things we would have never thought of that might be important at that very early stage.
“It’s given us a window into what’s going on at a molecular level, in a way we haven’t been able to do before.
It’ll allow us to look at what we can do, as public health doctors and parents, to improve a baby’s outlook according to what happens in these very first few days of life – and that will apply to a whole range of conditions, not just infectious diseases.
“It’s certainly very exciting to see where this new technology can take us.”
The paper, Dynamic molecular changes during the first week of human life follow a robust developmental trajectory, can be read here.
About the consortium
EPIC is an association of academic centres partnering to conduct systems biology studies in newborns and infants, comprised of investigators from the Boston Children’s Hospital (BCH), University of British Columbia (UBC), Medical Research Council Unit The Gambia (MRCG), The Kids Research Institute Australia, The University of Western Australia, the Papua New Guinea Institute for Medical Research (PNG-IMR), and Université libre de Bruxelles.
The consortium, which has its administrative hub within the Precision Vaccines Program at BCH, was established by Professor Levy in partnership with Professor Kollmann and Professor Kampmann.
Professor Richmond, Dr Van Den Biggelaar – a co-senior author on the paper – and Professor Pomat led the initial pilot study investigating vaccine responses in 30 newborns from Papua New Guinea. Another 30 newborns were involved in a second pilot study led by Professor Kampmann in The Gambia. The pilot data from these studies played a vital role in securing the $US10 million in funding from the National Institutes of Health (USA) that allowed the broader EPIC investigation to get under way.
About the Precision Vaccines Program
The Precision Vaccines Program, based at Boston Children’s Hospital and Directed by Dr. Ofer Levy, is a platform to enhance international collaboration between academia, government and industry to accelerate development of vaccines for vulnerable populations. The Program helped nucleate the Expanded Program on Immunization Consortium (EPIC), an affiliation of academic centres employing systems biology to study early life immunization.