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Recent analyzes indicate that pregnant women and newborns may face elevated risks of developing more severe cases of COVID-19 after SARS-CoV-2 infection.
New research led by researchers at Massachusetts General Hospital (MGH) and published in Cell reveals a lower than expected transfer of protective antibodies against SARS-CoV-2 through the placenta of infected mothers in the third trimester. The cause may be alterations in these antibodies after their production, a process called glycosylation.
The results expand on the team’s recent findings published in JAMA network open that pregnant women with COVID-19 do not transmit the SARS-CoV-2 virus, but also relatively low levels of antibodies against it, to newborns.
For this latest study, the scientists compared maternal antibodies to influenza (influenza), whooping cough (pertussis), and SARS-CoV-2, and how these antibodies transferred across the placenta.
Specific antibodies against influenza and pertussis were actively transferred in a relatively normal manner. In contrast, transfer of SARS-CoV-2-specific antibodies to the infant was not only significantly reduced, but transferred antibodies were less functional than influenza antibodies. Reduced transfer was only seen in third trimester infection.
Scientists found that altered binding of carbohydrates to specific SARS-CoV-2 antibodies, a process called glycosylation, may be to blame for this reduced transfer from mother to fetus in the third trimester. Carbohydrate binding in specific antibodies to SARS-CoV-2 in maternal blood were different from those observed in specific antibodies against influenza and pertussis.
This carbohydrate pattern can cause COVID-specific antibodies to “stick” in the maternal circulation, instead of being transferred across the placenta via placental antibody receptors.
Infection-induced increases in total maternal antibodies, as well as increased placental expression of an antibody receptor that attracts the carbohydrate pattern in SARS-CoV-2-specific antibodies, helped partially overcome the problem and facilitated transfer. of some functional antibodies from mother to fetus.
Interestingly, some of the antibodies that transferred the best were also the most functional, activating natural killer cells that could help the newborn fight the virus if exposed.
The findings have implications for the design of SARS-CoV-2 vaccines for pregnant women.
Vaccine regimens capable of boosting high levels of COVID-specific antibodies with placental-favored glycosylation patterns for selective transfer to the fetus may lead to better neonatal and infant protection. “
Andrea Edlow, MD, MSc, study co-senior and maternal-fetal medicine specialist at Authora, Massachusetts General Hospital
Edlow too assistant professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School.
Co-lead author and senior fellow at the Ragon Institute at MGH, MIT, and Harvard, Galit Alter, PhD, notes: “We are beginning to define the rules of SARS-CoV-2 placental antibody transfer for the first time – catalyzing our ability to rationally design vaccines to protect pregnant women and their newborns. “
In addition, understanding how antibody transfer varies by trimester may indicate critical windows in pregnancy that may be more desirable for vaccination to optimize protection for both mother and baby.
Source:
Massachusetts General Hospital
Magazine reference:
Atyeo, C., et al. (2020) Committed SARS-CoV-2 specific placental antibody transfer. Cell. doi.org/10.1016/j.cell.2020.12.027.
