Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection

Juliana Goncalves, Magda Melro, Marta Alenquer, Catarina Araújo, Júlia Castro-Neves, Nádia Charepe, Fátima Serrano, Carlos Pontinha, Maria João Amorim, Helena Soares*

*Corresponding author for this work

Research output: Working paperPreprint

Abstract

Maternal immune responses during pregnancy protect the growing fetus by clearing infection, preventing its vertical transmission, and through transplacental transfer of protective immune mediators to the fetus. How maternal immune response balances SARS-CoV-2 antiviral responses with transplacental transfer of protection to the fetus remains unclear. Our study shows that upon SARS-CoV-2 maternal infection, neutralizing antibodies (NAbs) are infrequently detected in cord blood. We uncovered that this is due to impaired IgG-NAbs placental transfer in symptomatic infection and to the predominance of maternal SARS-CoV-2 NAbs of the IgA and IgM isotypes, which are prevented from crossing the placenta. Crucially, the decision between favoring maternal antiviral response or transplacental transfer of immune protection to the fetus appears to hinge on the balance between IL-6 and IL-10 induced by SARS-CoV-2 infection, decreasing or increasing transplacental transfer of IgG-NAbs, respectively. In addition, IL-10 inversely correlates with maternal NK cell frequency. Finally, we found that ongoing infection favored perinatal transfer of maternal NK cells, highlighting a maternal sponsored mechanism to protect the newborn from horizontal transmission of infection. Our data point to an evolutionary trade-off which at once optimizes maternal viral clearance and vertical transfer of immune protection during the more susceptible perinatal period. Brief SummaryIn SARS-CoV-2 maternal infection, the balance between maternal antiviral response and transplacental transfer of cellular and humoral (NAb) protection hinges on maternal IL-6 and IL-10.
Original languageEnglish
Number of pages60
DOIs
Publication statusPublished - 23 Aug 2022
Externally publishedYes

Keywords

  • COVID-19
  • SARS-CoV-2
  • Pregnant
  • Vertical transmission
  • Maternal infection
  • Neutralizing antibodies
  • Neonatal immunity
  • Transplacental antibody transfer
  • NK cells

Fingerprint

Dive into the research topics of 'Balance between maternal antiviral response and placental transfer of protection in gestational SARS-CoV-2 infection'. Together they form a unique fingerprint.

Cite this