Early versus late third trimester maternal SARS-CoV-2 BNT162b2 mRNA immunization maximizes transplacental antibody transfer and neonatal neutralizing antibody levels

Rottenstreich, A.; Zarbiv, G.; Oiknine-Djian, E.; Vorontsov, O.; Zigron, R.; Kleinstern, G.; Wolf, D.; Porat, S.

Objective We aimed to assess the impact of early versus late third trimester maternal 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 during 27-36 weeks 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; median gestational age, 39.7 weeks): 83 (48.5%) immunized at early 3rd trimester (1st dose at 27-31 weeks), and 88 (51.5%) immunized at late 3rd trimester (1st 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 3rd trimester vaccination and were positively correlated with increasing time since vaccination (r= 0.26; P=0.001). The median placental transfer ratios of anti-S and anti-RBD specific IgG were increased following early versus late 3rd trimester immunization (anti-S ratio:1.3 vs. 0.9, anti-RBD-specific ratio:2.3 vs. 0.7, P<0.001). Neutralizing antibodies placental transfer ratio was greater following early versus late 3rd trimester immunization (1.9 vs. 0.8, P<0.001), and was positively associated with longer duration from vaccination (r= 0.77; P<0.001). Conclusions Early- as compared to 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 optimize neonatal seroprotection.