Pregnant women and neonates are at risk for adverse SARS CoV-2 infection outcomes, but few studies have evaluated this population for adaptive immunity. Here, we utilized samples collected from pregnant women 18 years or older reporting two or more respiratory symptoms. Information about trimester of COVID positive test or history of vaccination was also collected. Maternal blood (MB) samples were collected at prenatal clinic visits, or at delivery together with the fetal cord blood (CB)(n=70 dyads). Groups were selected based on trimester of infection, vaccination only, or no history of vaccination or infection (n=9–24) and compared with banked samples from a non-pregnant, age-matched woman from the same time period (n=7–12). Data shows IgG transfer to baby irrespective of trimester of infection (n=9–24 per group). Highest levels of antibodies were observed with vaccinated, uninfected women. Functional antibodies are transferred from mother to fetus following infection and vaccination. CD4 and CD8 T-cell activation and cytokine secretion were detected in maternal PBMCs, with highly variable expression between subjects. In at least one dyad with a PCR-confirmed infection during second trimester, both maternal and cord blood samples had low level expression of anti-S, N, RBD antibodies at delivery and the cord blood mononuclear cells showed CD4 T cell activation (CD134+) and cytokine secretion (IL-2, IL-6, TNFalpha) to spike antigens. These results indicate the unusual immunity to SARS CoV-2 infection during pregnancy and suggest at least one case of a neonate with anti-viral cellular immunity. Ongoing analyses and surveillance for perinatal outcomes may reveal how these immune responses impact infant respiratory outcomes.
Pregnancy is associated with a higher risk of adverse symptoms and outcomes for most infectious diseases, including SARS-CoV-2. These adverse risks are also observed in neonates. Antibodies provide protection against SARS-CoV-2 infection, and have been reported after maternal vaccination, maternal infection, and through passive transfer from mother to fetus in utero. However, it is unclear whether the magnitude or quality of maternally-derived fetal antibodies differs in the context of infection or vaccination. Here, we evaluated 93 paired maternal and neonatal umbilical cord blood plasma samples collected between October 2020 and February 2022 from a birth cohort of pregnant women from the greater New Orleans area. Histories of SARS-CoV-2 infection or vaccination were obtained. Humoral immunity was profiled for the levels of spike-specific antibodies and induction of antiviral humoral immune functions, including neutralization and Fc-mediated innate immune effector functions. We found that SARS-CoV-2 vaccination or infection during pregnancy increased the levels of antiviral antibodies from naïve subjects. Importantly, vaccinated mothers and cord samples had the highest anti-spike antibody levels and antiviral function independent of the time of vaccination during pregnancy. These results show that the most effective passive transfer of functional antibodies against SARS-CoV-2 in utero is achieved through vaccination, highlighting the importance of vaccination in pregnant women.
Supported by grants from NIH (NCI U54CA260581-02, NHLBI Grant HL-061007) and USDA (APHIS NBAF NSTP)
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