Pregnant women produce super antibodies to protect newborns, now scientists know how – ScienceDaily

Scientists discovered years ago that newborn babies depend on immune components passed on from their mothers to survive the pressure of pathogens that begin to invade their bodies immediately after birth. Eventually, children develop their own immune system, built up by surviving natural exposure to viruses and bacteria and supplemented by a phalanx of well-established childhood vaccines. But in the meantime, this is one of the most important gifts for mothers to keep their babies safe: antibodies.

Now, a comprehensive study published on June 8, 2022 nature, provides a surprising explanation of how these early days of maternal immunity actually work – and what this information might mean to prevent death and injury from a wide range of infectious diseases. The results show that researchers may be able to mimic the enhanced antibodies that expectant mothers produce to create new drugs to treat diseases, as well as improved vaccines to prevent them.

“For many years, scientists believed that antibodies could not enter cells. They did not have the necessary equipment. Thus, infections caused by pathogens that live exclusively inside cells were considered invisible to antibody-based therapies.” , says Sing Sing Way, MD, PhD, Department of Infectious Diseases at Cincinnati Children’s. “Our findings show that pregnancy changes the structure of certain sugars attached to antibodies, allowing them to protect babies from infection from a much wider range of pathogens.”

“The mother-baby dyad is so special. It’s the intimate relationship between a mother and her baby,” said John Erickson, MD, neonatologist and first author of the study.

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

Erickson continues: “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 newborn care units. This discovery paves the way for pioneering new therapies that can specifically target infections in pregnant mothers and newborn babies. I believe that these findings will also have far-reaching implications for antibody-based therapies in other areas. “

How mothers produce super antibodies

The new study identifies which specific sugars change during pregnancy, as well as how and when the change occurs. During pregnancy, the “acetylated” form of sialic acid (one of the sugars attached to antibodies) shifts to the “deacetylated” form. This very fine molecular change allows immunoglobulin G (IgG) – the most common type of antibody in the body – to take on an enhanced protective role by stimulating immunity through receptors that respond specifically to deacetylated sugars.

“This change is the light switch that allows maternal antibodies to protect babies from cell infection,” Wei said.

“Mothers always seem to know best,” Erickson added.

Renewed antibodies can be produced in the laboratory

Using advanced mass spectrometry techniques and other methods, the research team identified key biochemical differences between antibodies in virgin mice compared to pregnant mice. They also identified the enzyme naturally expressed during pregnancy that is responsible for driving this transformation.

In addition, the team successfully restored lost immune defenses by delivering laboratory-grown stocks of antibodies from healthy pregnant mice to infants born to mothers who have been genetically modified to lack the ability to remove acetylation from antibodies to improve protection.

Hundreds of monoclonal antibodies have been produced as potential treatments for a variety of diseases, including cancer, asthma, multiple sclerosis, and difficult-to-treat viral and bacterial infections – including new treatments quickly developed for COVID-19. Some have already been approved by the FDA, many others are in clinical trials, and some have failed to show strong results.

Wei says that the molecular change in antibodies that occurs naturally during pregnancy can be reproduced to change the way antibodies stimulate the immune system to refine its effects. This could potentially lead to improved treatment of infections caused by other intracellular pathogens, including HIV and respiratory syncytial virus (RSV), a common virus that poses a serious risk to infants.

Another reason to accelerate the development of vaccines

“We’ve known the long-term benefits of breastfeeding for years,” says Erickson. “One major factor is the transfer of antibodies to breast milk.”

The study shows that the molecular switch continues to exist in nursing mothers, so that antibodies with improved protective range are also transmitted to infants through breast milk.

Wei also says the findings underscore the importance of getting all available vaccines for women of childbearing age – as well as the need for researchers to develop more vaccines against infections that are particularly prevalent in women during pregnancy or in newborns.

“Immunity must exist in the mother in order to be passed on to her child,” Way said. “Without natural exposure or immunity enhanced by vaccination, when this light switch is turned over during pregnancy, there is no electricity behind it.”

About the study

A patent for modifying an antibody with sialic acid was filed by the Cincinnati Children’s Hospital with first author Erickson and senior author Way as inventors (PCT / US2022 / 018847).

In addition to Erickson and Way, the study in nature is a co-author of 9 researchers at Cincinnati Children’s and University of Cincinnati: Alexander Yaravsky, Bachelor’s degree, Ph.D. Janet LC Miller, Zu-Yu Shao, BS, Ashley Severance, Ph.D., Hillary Miller-Handley, MD, Yuehong Wu, MS Pham, PhD, Yueh-Chiang Hu, PhD, and Andrew Herr, PhD.

Collaborators also include experts from the University of Georgia, Ohio State University, Cornell University and the Roswell Park Complex Cancer Center in Buffalo.

Sources of funding include grants from the National Institutes of Health (F32AI145184x, K12HD028827, DP1AI131080, R01AI145840, R01AI124657, U01AI144673, T32DK007727, R714GM, R740MG, R714G, R714M, R714G; the program of the HHMI faculty; Burroughs’ Wellcome Fund; the March of Dimes Foundation, Ohio; and GlycoMIP, a platform for innovation in the materials of the National Science Foundation, funded by the Cooperation Agreement DMR-1933525.

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