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as observed during the SARS-CoV-2 global pandemic. Adverse outcomes can be mitigated by maternal vaccination, protecting the pregnant persons and the neonate or infant via passive transfer of maternal antibodies either in utero via the placenta or after birth via breastmilk.
Vaccination decisions during pregnancy are often influenced by a primary goal of protecting neonatal health. Thus, the decision to vaccinate during pregnancy or to delay vaccination is shaped by knowledge about the impact of vaccine timing and the duration of protection. Previous studies investigating maternal SARS-CoV-2 vaccination included minimal longitudinal sampling and focused on one aspect of antibody transfer (eg, maternal blood or breastmilk). In this study, we assessed the antibody response throughout gestation, at birth, and up to 12 months postpartum in a cohort of 121 women in maternal circulation, umbilical cord blood (UCB), newborn blood (NB), and breastmilk.
STUDY DESIGN: This study was approved by the institutional review boards of the Oregon Health & Science University and the University of Kentucky. From March 2021 until June 2022, maternal blood and breastmilk samples were obtained longitudinally from 121 SARS-CoV-2 vaccinated participants. The overwhelming majority (90.9%) of participants received the Pfizer BN162b2 vaccine (Table). UCB and maternal blood were collected at the time of delivery, whereas NB and colostrum were collected within 48 hours of delivery (Figure, A). An indirect enzyme-linked immunosorbent assay was used to determine the end-point titer (EPT) for IgG (total and subclasses) against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein in plasma, whereas breastmilk antibody levels were reported as optical density (OD) values.
Marshall. Maternal and neonatal antibody response to SARS-CoV-2 vaccination. Am J Obstet Gynecol MFM 2022.
Maternal age (y)
Gestational age at delivery (wk)
Fetal sex (% female)
Initial vaccine series
Days post second dose that the booster was received
Subjects were stratified by the trimester of initial maternal SARS-CoV-2 vaccination. Maternal age and gestational age at delivery are presented as mean ± standard deviation. There is no significant difference among maternal age or gestational age of delivery within the cohort when stratified by vaccination time point.
RESULTS: There was a strong inverse correlation between maternal plasma RBD-specific IgG titers and time elapsed since first vaccination (r=.07043; P<.0001; half-life, 56.45 days) (Figure, B). After the booster dose, RBD-specific IgG titers increased significantly (P<.0001) (Figure, C) and exhibited a longer half-life of 128.12 days (Figure, B and D). The booster produced a significant increase in all 4 IgG isotypes measured in maternal plasma (Figure, E).
The initial 2-dose vaccination regimen led to a detectable IgG antibody response in breastmilk (albeit at reduced levels when compared with the maternal plasma) with a half-life of 61.34 days (Figure, F). Comparable with the maternal circulation, the booster produced a significant increase in the antibody levels (P<.0001) (Figure, G) and half-life (124.67 days) (Figure, H). After the booster, IgG1 and IgG4 increased significantly, with IgG4 becoming dominant (Figure, I).
RBD-specific IgG antibodies were detected in the UCB plasma, albeit at significantly lower levels than in maternal circulation at delivery (P=.0012) (Figure, J). Interestingly, there was no correlation between the UCB RBD-specific IgG titers and the maternal titers at delivery (Figure, K) or the time since the first maternal vaccination (Figure, L). Although UCB is often used as a surrogate for NB, there may be differences in antibody transfer into the UCB and fetal circulation. As described for UCB, titers in NB were lower than those in maternal circulation at delivery (P=.0200) (Figure, M). In contrast to UCB, a significant positive correlation was observed between paired NB and maternal plasma titers at delivery (r=.3782; P≤.0001) (Figure, N). Moreover, NB titers were inversely correlated with the time since initial maternal vaccination (r=.3130; P=.0002) (Figure, O) with lower newborn IgG antibody titers in infants born to mothers vaccinated during early pregnancy.
CONCLUSION: Our results confirm that the initial 2-dose vaccination series administered during gestation led to an appreciable RBD-specific IgG response in maternal circulation, UCB, NB, and breastmilk. Longitudinal analysis of postpartum samples indicated that the booster dose is essential for eliciting higher and more durable antibody levels in both the maternal circulation and breastmilk. SARS-CoV-2–specific maternal antibodies generated via vaccination are passively transferred in utero and after birth via breastfeeding but wane within 6 months after the first vaccination dose. Our longitudinal data indicate that breastmilk antibody levels are dramatically increased by the booster. Therefore, the best neonatal protection against SARS-CoV-2 is for pregnant persons to receive the 3-dose vaccination series at any point during pregnancy to allow for placental antibody transfer and to subsequently breastfeed their children for at least 6 months, at which point infants are eligible for SARS-CoV-2 vaccination.
Continued breastfeeding throughout the first year of life is encouraged because SARS-CoV-2–specific maternal antibody levels persist in breastmilk following administration of the booster for at least 12 months.
Infections at the maternal-fetal interface: an overview of pathogenesis and defence.
This study was supported by grants from the National Institutes of Health under grant numbers R01AI145910 (to I.M.) and R01AI142841 (to I.M.). The funding source had no involvement in the study design; the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.
This study was presented at the 50th Annual Autumn Immunology Conference of Autumn Immunology, Inc, Chicago, IL, November 18–21, 2022.