Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine
Ofer Beharier, … , Michal Neeman, Michal Kovo
Ofer Beharier, … , Michal Neeman, Michal Kovo
Published May 20, 2021
Citation Information: J Clin Invest. 2021;131(13):e150319. https://doi.org/10.1172/JCI150319.
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Clinical Research and Public Health Reproductive biology

Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine

Abstract

BACKGROUND The significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of the BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection.METHODS A multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to 3 study groups: vaccinated (n = 86); PCR-confirmed SARS-CoV-2 infected during pregnancy (n = 65), and unvaccinated noninfected controls (n = 62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using the Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD, and N).RESULTS The BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer ratio at birth was significantly lower for third-trimester as compared with second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group.CONCLUSION Antenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy.FUNDING Israel Science Foundation and the Weizmann Institute Fondazione Henry Krenter.

Authors

Ofer Beharier, Romina Plitman Mayo, Tal Raz, Kira Nahum Sacks, Letizia Schreiber, Yael Suissa-Cohen, Rony Chen, Rachel Gomez-Tolub, Eran Hadar, Rinat Gabbay-Benziv, Yuval Jaffe Moshkovich, Tal Biron-Shental, Gil Shechter-Maor, Sivan Farladansky-Gershnabel, Hen Yitzhak Sela, Hedi Benyamini-Raischer, Nitzan D. Sela, Debra Goldman-Wohl, Ziv Shulman, Ariel Many, Haim Barr, Simcha Yagel, Michal Neeman, Michal Kovo

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Figure 3

Dependence of immune response to SARS-CoV-2 infection and to vaccination on the duration from exposure to delivery.

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Dependence of immune response to SARS-CoV-2 infection and to vaccination...
(A) Analysis of the level of maternal IgG at delivery for acute (<50 days) infection. Time was derived from the GA of RT-PCR positivity and the GA of delivery (see the immune response across pregnancy in Figure 1). (B) Analysis of maternal IgG response to BNT162b2 vaccination derived from the GA of the first vaccine and the GA of delivery. (C) Analysis of the level of fetal IgG at delivery, following BNT162b2 vaccination. Time was derived from the GA of the first vaccine and the GA of delivery. (B and C) A second dose was administered on day 21. Shaded areas and lines in A–C show the mean and 95% confidence interval. (D) Serological data of maternal-fetal pairs were derived from control, unvaccinated serologically negative (N–) mothers; as well as vaccinated mothers grouped for deliveries in the first 3 weeks after the first vaccine; deliveries during the first week after the second vaccine; and fully vaccinated who delivered more than a week after the second vaccine. Left columns, IgG; right columns, IgM; from top to bottom, serological response to S1, S2, RBD, and N. Statistical significance: †,‡,§ above the blue bars indicate significant differences among the groups in maternal antibodies, while ††,‡‡,§§ above the orange bars indicate significant differences among the groups in fetal antibodies (Kruskal-Wallis 1-way ANOVA test, following by Dunn’s all-pairwise comparisons test). An asterisk indicates a significant difference between maternal and fetal antibodies within the same group (paired t test). Box and whiskers: middle line, median; box, the 25% and 75% (25th and 75th percentiles); whiskers, minimum & maximum values (Supplemental Table 2).