New research conducted by researchers at Massachusetts General Hospital (MGH) and published in Cell shows lower than expected transmission of protective SARS-CoV-2 antibodies across the placenta of mothers infected in the third trimester. This can be caused by changes in these antibodies after they have been made – a process known as glycosylation.
The results expand on the team’s recent findings, published in JAMA Network Open, that pregnant women with Covid-19 do not pass the SARS-CoV-2 virus, but also relatively low levels of antibodies against newborns to newborns.
For this latest study, scientists compared maternal antibodies to influenza, whooping cough (pertussis), and SARS-CoV-2 and how these antibodies were transmitted across the placenta.
Influenza and pertussis specific antibodies were actively transferred in a relatively normal manner. In contrast, the transmission of SARS-CoV-2-specific antibodies to the baby was not only significantly reduced, but the antibodies transferred were also less functional than the antibodies against influenza. The decreased transmission was only seen with infection in the third trimester.
The scientists found that altered binding of carbohydrates to the SARS-CoV-2-specific antibodies – a process known as glycosylation – could be responsible for this decreased transfer from mother to fetus in the third trimester.
The carbohydrate accumulations on SARS-CoV-2-specific antibodies in maternal blood differed from those on influenza and pertussis-specific antibodies. This carbohydrate pattern can lead to the Covid-specific antibodies “getting stuck” in the maternal circulation and not being transmitted via placenta antibody receptors via the placenta.
Infection-related increases in total maternal antibodies, as well as higher placental expression of an antibody receptor that attracts the carbohydrate pattern on the SARS-CoV-2 specific antibodies, helped to partially overcome the problem and facilitate the transfer of some functional antibodies from mother to fetus.
Interestingly, some of the antibodies that were best transferred were also the most functional and activating natural killer cells that could help the newborn fight the virus if exposed.
The results have implications for the design of vaccines against SARS-CoV-2 for pregnant women.
“Vaccination regimens that are able to control high levels of Covid-specific antibodies with glycosylation patterns preferred by the placenta for selective transmission to the fetus can result in better protection for newborns and infants,” said Andrea Edlow , Co-Senior Author, MD, MSc, a Specialist in Maternal-Fetal Medicine at MGH and Assistant Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School.
“We are beginning to define the rules for the transfer of SARS-CoV-2 with placenta antibodies for the first time. This catalyzes our ability to rationally design vaccines to protect pregnant women and their newborns,” said co-senior author and a core member of the Ragon Institute of MGH, MIT, and Harvard, Galit Alter, PhD, said.
In addition, understanding how antibody transfer changes across trimesters can point to critical windows in pregnancy that may be most desirable for vaccination to optimize protection for both mother and child.