Selective transfer of maternal antibodies in preterm and fullterm children

Abstract

Preterm newborns are more likely to suffer from infectious diseases at birth compared to children delivered at term. Whether this is due to compromised cellular, humoral, or organ-specific development remains unclear. To begin to define whether maternal–fetal antibody transfer profiles differ across preterm (PT) and fullterm (FT) infants, the overall quantity and functional quality of an array of 24 vaccine-, endemic pathogen-, and common antigen-specific antibodies were assessed across a cohort of 11 PT and 12 term-delivered maternal:infant pairs from birth through week 12. While total IgG levels to influenza, pneumo, measles, rubella, EBV, and RSV were higher in FT newborns, selective Fc-receptor binding antibodies was noted in PT newborns. In fact, near equivalent antibody-effector functions were observed across PT and FT infants, despite significant quantitative differences in transferred antibody levels. Moreover, temporal transfer analysis revealed the selective early transfer of FcRn, FcγR2, and FcγR3 binding antibodies, pointing to differential placental sieving mechanisms across gestation. These data point to selectivity in placental transfer at distinct gestational ages, to ensure that children are endowed with the most robust humoral immunity even if born preterm.

Diverging maternal and infant cord antibody functions from SARS-CoV-2 infection and vaccination in pregnancy

“…Fc effector functions may be particularly relevant for the fetus. Similar to HIV, CMV and malaria and some vaccines (67)(68)(69)92), the data from this study show that Fcg receptor mediated functions are transferred along with IgG across the placenta (Figure 1, 3). Higher natural killer cell activation and cellular phagocytosis in cord compared to paired maternal samples (Figure 3B, D) irrespective of immune exposure suggest preferential transport of Fcg functions that contrast equivalent levels of neutralizing (Figure 3A) and complement (Figure 3C) activities.…”

“…Sex (82,83), infant prematurity (69), trimester of vaccination (31,33), mRNA vaccine platform (27,33) and disease severity (45,46,84) impact antibody responses. Though limited by power, no significant differences were observed in these data.…”

“…Moreover, antibody functional potency, breadth and coordination between neutralizing and Fc effector responses likely contribute to protection (26,(53)(54)(55)(56)(57). Some data demonstrate that maternal immune adaptation to pregnancy alters antibody subclass and glycosylation (30,(58)(59)(60)(61)(62)(63)(64)(65), but the implications for antibody functions and what exists for the fetus are only just beginning to be appreciated (66)(67)(68)(69)(70).…”

Distinct Type 1 Immune Networks Underlie the Severity of Restrictive Lung Disease after COVID-19

“…Given that these models select a minimal set of features that are most distinct between groups 100 , we next identified co-correlates of model-selected features that may contribute equally to group separation. 101,102 Pearson correlation networks were generated using the same data as elastic net and OPLS-DA analyses (patient group and healthy control together)(R, v4.3.1; RStudio, v2023.09.1-494). Highly correlated features (Pearson R >0.8, FDR-adjusted p <0.05) were included in correlation networks centered around the elastic net-selected features, and visualized using Cytoscape (version 3.10.0).…”

“…Co-correlate Networks: Given that these models select a minimal set of features that are most distinct between groups 100 , we next identified co-correlates of model-selected features that may contribute equally to group separation. 101,102 Pearson correlation networks were generated using the same data as elastic net and OPLS-DA analyses (patient group and healthy control together)(R, v4. RStudio, v2023.09.1-494).…”