What if you could lower the risk that newborns would develop life-threatening infections? Optimize — even personalize — the timing of vaccines given early in life? Figure out which babies aren’t developing competent immune systems or are at risk of type 1 diabetes? What if you could give them an immunological tweak to steer them back onto a healthy track?
New research suggests those “what ifs?” may someday be reality.
A study published Tuesday, from researchers at Boston Children’s Hospital and colleagues in several other countries, used minute amounts of blood drawn in the first week of life to better understand what happens to the immune system in the hours and days after birth. The primary finding — that there are discernible and consistent patterns of change that occur — point to exciting possibilities, researchers believe.
The study, published in the journal Nature Communications, is based on data from 60 babies in Gambia and Papua New Guinea. Remarkably, the data correspond with findings of a study of 100 babies in Stockholm, Sweden, that was published last summer.
Petter Brodin, a pediatric immunologist at the Karolinska Institutet in Stockholm and the senior author of the Swedish study, said he found the similarities intriguing.
“For me, it’s reassuring because it fits with this idea that there’s a stereotypic immune system development in all children,” said Brodin, who was not involved in the new research.
Both studies involved drawing and analyzing blood from newborns. Given their fragile state and the small volumes of blood their tiny bodies hold, ethics committees have traditionally been reluctant to allow scientists to draw much blood from newborns for research purposes.
But today’s testing systems can extract large quantities of information from minuscule amounts of blood. The new study, for instance, relied on blood draws of less than a quarter-teaspoon of blood. The researchers were given ethical approval to make two blood draws from each infant in the study, at birth and again on either day 1, day 3, or day 7.
The study they have published reports on the system they devised for gathering large amounts of data from these tiny blood draws, using techniques developed by some of co-authors who work at the University of British Columbia.
Comparing the two samples from each baby allowed the researchers to track which of thousands of genes were being activated and which proteins were being made, as well as other changes.
The findings will help establish a baseline with which to assess what should happen to the immune system in the earliest part of life, said Dr. Ofer Levy, a pediatric infectious diseases specialist at Boston Children’s and one of the senior authors of the study.
“You don’t want to just measure a lot of stuff. You want to understand it relative to something we care about clinically,” Levy told STAT. “Because more and more evidence points to the fact that what happens to us early in life and the trajectory we go on can impact health, it can impact the risk of disease, including infection, and is really critical.”
“Now that we’ve shown we can do this, we can use this technique and approach to optimize vaccines and other interventions … to reduce infection and enhance health in early life,” he said.
The study in Gambia was effectively a pilot, to see if it worked. The data drawn from the blood of the babies from Papua New Guinea validated the pilot’s findings.
Why start in Gambia? In the United States, only one vaccine is given at birth; it protects against hepatitis B.
But in countries where tuberculosis is common, such as Gambia, babies are given the TB vaccine BCG (short for Bacillus Calmette-Guérin vaccine) at birth as well. BCG is a live bacterial vaccine, and this type of vaccine generally induces broader protection than vaccines made with an inactivated pathogen.
Levy said the research group wants to see if newborns who get BCG vaccine have an enhanced response to the hepatitis B vaccine. A larger, follow-up clinical trial will look at the question, giving some newborns no vaccines for the first week of life (they will be caught up after), hepatitis B or BCG only, or both vaccines.
The same approach could be used to study a number of questions about early development, Levy said, such as how infections or, say, different modes of feeding — breast versus bottle — affect the immune system.
Brodin said there has been a push to try to better understand what happens to babies’ immune systems in the months and years after birth. Much of the previous work in this area was conducted either on blood from umbilical cords or from mice.
But Brodin said he believes these types of studies will help scientists understand which infants are susceptible to dangerous early-life infections and which may go on to develop an immune disorder. And that could help scientists develop better interventions.
The study in Sweden and the one in Gambia and Papua New Guinea were not identical. Brodin’s group studied infants for longer — out to three months after birth. Levy’s group set out to measure more types of early changes.
Brodin studied blood from infants born in a city in a developed country while Levy studied blood from babies born in two different developing world settings. The cohort of Swedish babies included full-term and premature infants. Some were born by vaginal birth, others by cesarean section.
Yet the fact that the two groups saw many similar findings strengthens the argument that immune systems develop along common pathways.
“This common trajectory is exciting as it allows us to ask bigger questions about the differences between different populations and the impact of biomedical interventions such as vaccines on development,” Levy said.
— An earlier version of this story incorrectly described BCG vaccine.