Abstract
SummarySARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third-trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.
Highlights
Over 44,000 pregnant women in the U.S have been infected with SARS-CoV-2, and, with an estimated 140 million births annually worldwide, the number of pregnant women infected this year alone is likely in the millions (CDC, 2020)
Previous work has shown that both newborns and pregnant women are susceptible to respiratory infections, including influenza and respiratory syncytial virus (RSV) (Zaman et al, 2008; Rasmussen et al, 2012; Gerretsen and Sande, 2017; 628 Cell 184, 628–642, February 4, 2021 a 2020 The Author(s)
SARS-CoV-2-specific antibodies are transferred inefficiently to the neonate Past reports have described infection-driven alterations in placental immunoglobulin G (IgG) transfer to the neonate (Okoko et al, 2001; Farquhar et al, 2005; Cumberland et al, 2007; Ogolla et al, 2015; Martinez et al, 2019), but it is unclear whether placental transfer dynamics shift with SARS-CoV-2 infection
Summary
Over 44,000 pregnant women in the U.S have been infected with SARS-CoV-2, and, with an estimated 140 million births annually worldwide, the number of pregnant women infected this year alone is likely in the millions (CDC, 2020). Up to 16% of pregnant women test positive for SARS-CoV-2 in geographic hotspots (Breslin et al, 2020; Sutton et al, 2020), pregnant women and neonates are excluded from vaccine and therapeutic trials due to enhanced safety standards required for this population. Recent data demonstrate that a greater proportion of neonates and infants have severe or critical illness upon SARS-CoV-2 infection compared to older pediatric counterparts (Kim et al, 2020; Dong et al, 2020). Given the immature nature of the newborn’s immune system, coupled with anticipated delays in vaccine deployment to pregnant women and children, infants are highly vulnerable during the SARS-CoV-2 pandemic
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