Vaccines are considered one of the most groundbreaking interventions in medicine. Before vaccines, hundreds of thousands of people died each year due to diseases like whooping cough, measles and the flu. However, some vaccines can only be delivered after a child reaches a certain age, leaving infants more vulnerable than most.

But thanks to their mothers, infants are not completely without protection. Throughout pregnancy, mothers transfer nutrients and immune cells to their child via the placenta, and it is these cells that serve as the base for the child’s immune system.

A research team at the Ragon Institute of MGH, MIT and Harvard led by Galit Alter, PhD, Samana Cay MGH Research Scholar 2017-2022, decided to learn more about the selection and transfer process with the hope of increasing the protection that babies receive before birth.

Why studying antibody transfer is important

During pregnancy, mothers transfer immune cells that are effective against certain diseases like measles, but antibodies for other dangerous diseases like polio are less efficiently transferred.

Many people opt to have their children vaccinated once they are old enough to provide more complete protection, but what about the period in between birth and vaccination?

Vaccinating newborns earlier is not an option due to health risks and regulations, but vaccinating expecting mothers could be a possibility. If scientists could figure out how antibody transfer works during pregnancy, there is a chance they could create a new form of maternal vaccine that could help bolster a child’s immune system before birth.

A novel tool for antibody profiling

Most people think of the immune system as something that simply fights infections, but the immune system carries out many more complex functions scientists are still learning about.

There are roughly 10³² antibodies in any given person that are designed to target a variety of microbes, viruses and other harmful substances, and each day those antibodies are modified and replenished. To uncover more about the function and mechanisms behind these antibodies, Alter and the research team used a novel proprietary tool, Systems Serology, to profile them.

The tool works similarly to facial recognition software by identifying patterns within a given set of information. Once researchers collected blood samples from the mothers, they used a machine learning algorithm to identify patterns that may be significant.

What they discovered

They found that the placenta successfully filtered out and transferred the cells that activate natural killer (NK) cells, one of the major building blocks of the innate immune system. NK cells are lymphocytes in the same family as T and B cells, and are known for their ability to kill virally infected cells and tumor cells without being primed to do so, making them some of the most functional immune cells to have during the first days of life.

Researchers also identified mechanisms that appear to regulate which cells the placenta selects, which could be key in developing improved maternal vaccines. Using the “blueprint” developed using the systems serology tool, researchers may be able to actively induce certain antibodies to the baby through their mother.

“For the first time we are starting to understand how the immune system is really working, and how antibodies are leveraging and directing immune function. It allows us to think about how we can make vaccines in a completely new way, really fundamentally driven by our basic understanding of how antibodies are fighting the diseases.”

Galit Alter, PhD

What this could mean for other diseases

The systems serology tool can be applied very broadly to diseases where antibodies play a helpful or harmful role, but at the moment it is easier to work with antibodies linked disease-causing pathogens rather than autoimmune diseases or cancer, says Alter.

“The nice thing about pathogens is you know what the antigen target is because they are so different than us, so we can profile antibodies to those targets quite easily. When you get into autoimmune diseases or cancer, it becomes more difficult because you don’t know what the immune system is targeting.”

Galit Alter, PhD

However, this is not to say using this technology for autoimmune diseases and cancer is impossible. Alter believes these studies are just the tip of the iceberg and, since technology evolves so quickly, there’s no telling what scientists could learn from these tools in the future.

“This technology is accelerating our ability to develop better drugs and better vaccines for diseases for which we are currently not able to prevent.”

Galit Alter, PhD

Dr. Alter is a Samana Cay MGH Research Scholar 2017-2022 and a Kristine and Bob Higgins MGH Research Scholar 2012-2017. Learn more about the MGH Research Scholars.

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