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

Abstract

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.

Keywords: Cord blood; Coronavirus disease 2019; Passive immunity; Pregnancy; Serology; Severe acute respiratory syndrome coronavirus 2; Vaccination.

Fig. 1

Schematic flow chart of patient inclusion in the study.

Fig. 2

SARS-CoV-2 anti-S (a) and anti-RBD-specific (b) IgG levels in maternal sera were positively correlated to their respective concentrations in cord blood (r = 0.78; P  < 0.001 and r= 0.66; P  < 0.001, respectively). Maternal anti-S (c) and anti-RBD-specific (d) IgG concentrations were negatively associated with the time lapsed since immunization (r =  −0.37; P  < 0.001 and r =  −0.41; P  < 0.001, respectively). Correlations, as well as correspondent R and P values were calculated by Pearson's test, as shown in each panel. The dotted lines are the 95% confidence intervals..

Fig. 3

Neonatal concentrations of anti-S (a) IgG antibodies did not differ in relation to maternal third trimester immunization timing (P = 0.80). Anti-RBD-specific (b) IgG concentrations in neonatal sera were positively correlated with increasing time since vaccination (r =  0.26; P = 0.001). Placental transfer ratios of anti-S (c) and anti-RBD-specific (d) IgG were directly associated with longer duration since immunization (r =  0.49; P  < 0.001 and r= 0.83; P  < 0.001, respectively). Correlations, as well as correspondent R and P values were calculated by Pearson's test, as shown in each panel. The dotted lines are the 95% confidence intervals.

Fig. 4

Maternal sera neutralizing activity (a) and neonatal anti-RBD concentrations (b) were positively correlated to neonatal sera neutralizing activity (r =  0.43; P = 0.01 and r =  0.68; P < 0.001, respectively). Duration of time since vaccination (c) and anti-RBD placental transfer ratio (d) were positively associated with neutralizing antibodies placental transfer ratio (r =  0.77; P < 0.001 and r =  0.82; P < 0.001, respectively). Neutralizing activity is reflected by NT₅₀ values (see Methods section).

Fig. S1Anti-RBD-specific (a) IgG neonatal concentrations and placental transfer ratio (b) in relation to gestational age at the time of vaccination.