Maternal-neonatal transfer of SARS-CoV-2 immunoglobulin G antibodies among parturient women treated with BNT162b2 messenger RNA vaccine during pregnancy

Abstract

Background The exclusion of pregnant women from COVID-19 mRNA vaccine trials raised hesitancy regarding the benefit of vaccination of pregnant women, hence little is known about the vaccine's efficacy in this population. Objective To determine the maternal-neonatal transplacental transfer of SARS CoV-2 antibodies among vaccinated parturient women. A control group of COVID 19 recovered patients was included in order to compare IgG levels between vaccinated and recovered patients. Study Design A prospective cohort study in a single tertiary medical center in Israel between February and March 2021; parturient women who had been vaccinated with BNT162B2 mRNA vaccine during pregnancy were included and compared to COVID-19 recovered parturient women. SARS CoV-2 IgG antibodies were measured in maternal and cord sera, dried blood spot samples taken from newborns, and breast-milk samples. The primary outcome was to determine whether neonatal cord and dried blood spot samples were positive for SARS CoV-2 antibodies and to evaluate transfer ratio defined as cord blood IgG divided by maternal IgG levels. Results The study included 64 vaccinated parturient women and 11 parturient women who had COVID-19 disease during pregnancy. All maternal blood sera samples and 98.3% of cord blood sera samples were positive for SARS Cov-2 IgG with median concentrations of 26.1 (IQR 22.0;39.7) and 20.2 (IQR 12.7;29.0) respectively. Similarly, 96.4% of neonatal blood spot samples and all breast milk samples were positive for SARS CoV-2 IgG with median concentrations of 11.0 (IQR 7.2;12.8) and 4.9 (IQR 3.8;6.0), respectively. There was a significant positive correlation between maternal serum levels of SARS Cov-2 IgG and cord blood (R=0.483, p=0.0001), neonatal blood spot (R=0.515, p=0.004), and breast milk levels (R=0.396, p=0.005) of SARS CoV-2 IgG. The median placental transfer ratio of SARS-COV-2 IgG was 0.77. Comparison of vaccinated with recovered COVID-19 patients revealed significantly higher SARS CoV-2 IgG levels in maternal serum and cord blood among vaccinated women (p<0.0001). Conclusion(s) Our study demonstrated efficient transfer of SARS CoV-2 IgG across the placenta from women vaccinated with BNT162b2 mRNA vaccine during pregnancy to their neonates with positive correlation between maternal serum and cord blood antibody concentrations. In addition to maternal protection against COVID-19, the vaccine may also provide neonatal humoral immunity.

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and early infancy

“…We found that the timing of immunization during pregnancy is important to ensure transplacental transfer of protective antibodies to the neonate, and during critical windows of immune vulnerability during early infancy. Consistent with prior studies showing robust immune responses to mRNA vaccination 14,15,17 , we found high levels of IgG after two doses of mRNA vaccine. However, completion of the vaccination series well before delivery was important to ensure transfer of antibodies to the infant.…”

“…Similar to prior studies 14,15,17 , we found that mRNA vaccination during pregnancy led to an increase in anti-SARS-Cov-2 IgG following dose 1 (n=7, mean 388.6, SD 224.8 RFU) and an even further robust increase after vaccination dose 2 (n=12, mean 3214, SD 1383 RFU). Anti-SARS-CoV-2 IgM (n=7, mean 53.3, SD 50.2 RFU) was detected in two maternal participants following dose 1, but only 1 participant following dose 2 (n=12, mean 23.8, SD 17 RFU, Fig 1).…”

“…In addition to protecting the mother against severe disease, vaccination during pregnancy may protect the newborn through passive transfer of maternal immunoglobulin. SARS-CoV-2 infection and vaccination during pregnancy produces an IgG response that is transferred to the fetus [10][11][12][13][14][15][16] . Evidence of newborn protection might help address maternal concerns about adverse effects.…”

Passive Immunity to SARS-CoV-2 at Birth Induced by Vaccination in the First Trimester of Pregnancy

“…In agreement with other recent studies, we have observed that the anti-SARS-CoV-2 vaccine transfers antibody immunity to the fetus through the placental barrier, revealing IgG anti-SARS-CoV-2 on neonatal blood samples [ 11 , 12 , 23 ].…”

Effectiveness of Maternal Vaccination with mRNA COVID-19 Vaccine During Pregnancy Against COVID-19–Associated Hospitalization in Infants Aged <6 Months — 17 States, July 2021–January 2022

“…Evidence from other vaccine-preventable diseases suggests that maternal immunization can provide protection to infants, especially during the high-risk first 6 months of life, through passive transplacental antibody transfer (2). Recent studies of COVID-19 vaccination during pregnancy suggest the possibility of transplacental transfer of SARS-CoV-2-specific antibodies that might provide protection to infants (3)(4)(5); however, no epidemiologic evidence currently exists for the protective benefits of maternal immunization during pregnancy against COVID-19 in infants. The Overcoming COVID-19 network conducted a test-negative, case-control study at 20 pediatric hospitals in 17 states during July 1, 2021-January 17, 2022, to assess effectiveness of maternal completion of a 2-dose primary mRNA COVID-19 vaccination series during pregnancy against COVID-19 hospitalization in infants.…”