Timing of SARS-CoV-2 vaccination during the third trimester of pregnancy and transplacental antibody transfer: a prospective cohort study

Objective: We aimed to assess the impact of early versus late third-trimester maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination on transplacental transfer and neonatal levels of SARS-CoV-2 antibodies. Methods: Maternal and cord blood sera were collected following term delivery after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination, with the first vaccine dose administered between 27 and 36 weeks of gestation. SARS-CoV-2 spike protein (S) and receptor-binding domain (RBD) -specific, IgG levels and neutralizing potency were evaluated in maternal and cord blood samples. Results: The study cohort consisted of 171 parturients—median age 31 years (interquartile range (IQR) 27–35 years); median gestational age 39⁺⁵ weeks (IQR 38⁺⁵–40⁺⁴ weeks)–83 (48.5%) were immunized in early thrird-trimester (first dose at 27–31 weeks) and 88 (51.5%) were immunized in late third trimester (first dose at 32–36 weeks). All mother–infant paired sera were positive for anti S- and anti-RBD-specific IgG. Anti-RBD-specific IgG concentrations in neonatal sera were higher following early versus late third-trimester vaccination (median 9620 AU/mL (IQR 5131–15332 AU/mL) versus 6697 AU/mL (IQR 3157–14731 AU/mL), p 0.02), and were positively correlated with increasing time since vaccination (r = 0.26; p 0.001). Median antibody placental transfer ratios were increased following early versus late third-trimester immunization (anti-S ratio: 1.3 (IQR 1.1–1.6) versus 0.9 (IQR 0.6–1.1); anti-RBD-specific ratio: 2.3 (IQR 1.7–3.0) versus 0.7 (IQR 0.5–1.2), p < 0.001). Neutralizing antibodies placental transfer ratio was greater following early versus late third-trimester immunization (median 1.9 (IQR 1.7–2.5) versus 0.8 (IQR 0.5–1.1), p < 0.001), and was positively associated with longer duration from vaccination (r = 0.77; p < 0.001). Conclusions: Early compared with late third-trimester maternal SARS-CoV-2 immunization enhanced transplacental antibody transfer and increased neonatal neutralizing antibody levels. Our findings highlight that vaccination of pregnant women early in the third trimester may enhance neonatal seroprotection.