Pregnant women make super antibodies to protect newborns, now scientists know how

Scientists discovered years ago that newborns depend on immune components transferred from their mothers to ward off attack from pathogens that begin to invade their bodies as soon as they are born. Eventually, children develop their own immune systems, built up through natural exposure to viruses and bacteria, and augmented by a phalanx of well-established childhood vaccines. But in the meantime, it’s one of mom’s most important gifts that keeps her babies safe: antibodies.

Now, a far-reaching study published on June 8, 2022 Nature, Provides a surprising explanation of how those early days of mom-provided immunity actually work—and what that information could mean for preventing death and disability from a wide range of infectious diseases. The findings suggest that researchers may be able to mimic the amped-up antibodies that expect mothers will need to create new drugs to treat diseases as well as better vaccines to prevent them.

“For many years, scientists believed that antibodies could not move inside cells. They did not have the necessary machinery. And therefore, infections caused by pathogens that live exclusively inside cells, antibody-based treatments were believed to be invisible,” says Sing Sing Way, MD, PhD, of the Division of Infectious Diseases at Cincinnati Children’s. “Our findings suggest that pregnancy alters the structure of some sugars associated with antibodies, which allows them to protect babies from infection by a wide range of pathogens.”

“Mother-infant coloration is very special. It’s a close bond between a mother and her child,” says John Erickson, MD, PhD, in the Department of Neonatology, and first author of the study.

He and Erickson are both part of the Cincinnati Children’s Center for Inflammation and Tolerance and the Perinatal Institute, which strives to improve outcomes for all pregnant women and their newborns.

Erikson adds, “This special relationship begins when babies are in the womb and continues after birth. I love seeing the closeness between mothers and their babies in our neonatal care units. paves the way for therapies that can specifically target infections. Pregnant mothers and newborns. I believe these findings will have far-reaching implications for antibody-based therapies in other areas as well.”

How Mothers Make Super Antibodies

The new study identifies which specific sugars are changed during pregnancy, as well as how and when the changes happen. During pregnancy, the “acetylated” form of sialic acid (one of the sugars attached to the antibody) changes to the “deacetylated” form. This very subtle molecular change allows immunoglobulin G (IgG) – the body’s most common type of antibody – to play an extended protective role by stimulating immunity through receptors that specifically respond to deacetylated sugars.

“This change is the light switch that allows maternal antibodies to protect the babies against infection inside the cells,” he says.

“Moms always feel best,” Erikson says.

Modified antibodies can be produced in the laboratory

Using advanced mass spectrometry techniques and other methods, the research team narrowed down the major biochemical differences between antibodies in virgin mice compared to pregnant mice. They also identified an enzyme naturally expressed during pregnancy responsible for driving this change.

In addition, the team successfully restored the lost immune protection by supplying a laboratory-grown supply of antibodies from healthy pregnant mice to puppies born to mothers who needed the ability to remove acetylation from antibodies to enhance protection. The deficiency was gene-edited.

Hundreds of monoclonal antibodies have been produced as potential treatments for a variety of disorders, including cancer, asthma, multiple sclerosis, as well as hard-to-shake viral and bacterial infections – including rapidly developing new treatments for COVID-19. Some are already approved by the FDA, many more are in clinical trials, and some have failed to show strong results.

They say that the molecular changes of naturally occurring antibodies during pregnancy can be replicated to alter how the antibodies stimulate the immune system to exert their effects. This could potentially lead to better treatments for infections caused by other intracellular pathogens including HIV and respiratory syncytial virus (RSV), a common virus that poses serious risks to infants.

Another reason to accelerate vaccine development

“We’ve known about the many far-reaching benefits of breastfeeding for years,” Erickson says. “A major factor is the transfer of antibodies into breast milk.”

The study suggests that the molecular switch persists in nursing mothers so that even antibodies with increased protective properties can be transferred to infants through breast milk.

Additionally, they say the findings underscore the importance of getting all available vaccines for women of reproductive age — as well as the need for researchers to develop even more vaccines against infections that can occur during pregnancy or in newborns. are particularly prominent among women.

“The immunity must exist within the mother in order to be transferred to her child,” he says. “Without immunity due to natural exposure or vaccination, when that light switch is flipped during pregnancy, there’s no electricity behind it.”

about study

A patent on antibody sialic acid modification has been filed by Cincinnati Children’s Hospital with first author Erikson and senior author Way as the inventor (PCT/US2022/018847).

In addition to Erickson & Way, study in Nature Co-authored by 9 researchers from Cincinnati Children’s and University of Cincinnati were: Alexander Yarawski, BS, Janet LC Miller, PhD, Tzu-Yu Shao, BS, Ashley Severance, PhD, Hilary Miller-Handley, MD, Yuhong Wu, MS, Jiang Pham, PhD, Yuh-Chiang Hu, PhD, and Andrew Herr, PhD.

Contributors also included experts from the University of Georgia, The Ohio State University, Cornell University and the Roswell Park Comprehensive Cancer Center in Buffalo.

Funding sources included grants from the National Institutes of Health (F32AI145184x, K12HD028827, DP1AI131080, R01AI145840, R01AI124657, U01AI144673, T32DK007727, R24GM137782, R01GM094363, and R01AI162964); HHMI Faculty Scholar Program; Burroughs Welcome Fund; March of Dimes Foundation Ohio Collaborative; and GlycoMIP, a National Science Foundation materials innovation platform funded through cooperative agreement DMR-1933525.