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

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. We evaluated the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during pregnancy. We found no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we found time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persisted during early infancy. Additionally, using phage immunoprecipitation sequencing, we found a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. In conclusion, products of mRNA vaccines are not transferred to the fetus during pregnancy, however timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.


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Growing evidence has shown that pregnant individuals are at higher risk for SARS-CoV-50 2-related morbidity and mortality 1-4 . Despite this, vaccination uptake by pregnant individuals has 51 been slower than the general population 5 , in part because of maternal concern of adverse 52 effects on the embryo or fetus, even with strong consensus recommendations for COVID-19 53 vaccination prior to or during pregnancy from several medical societies 6 . Pregnant individuals 54 were excluded from initial vaccine trials, and complete data on safety, efficacy, optimal timing of 55 the vaccine in pregnancy, or its impact on the fetus has been delayed 7 , which may impact 56 individual medical decision making. Current COVID-19 vaccines fully approved and under 57 emergency use in the United States include the mRNA vaccines BNT-162b2 and mRNA-1273, 58 which target the SARS-CoV-2 Spike protein and stimulate protective immune responses 8,9 . In 59 addition to protecting the mother against severe disease, vaccination during pregnancy may    Table S1.

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Vaccine mRNA products do not cross the placenta

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To determine the transplacental transfer of mRNA vaccine derived products, we 89 examined available maternal blood at delivery, placenta tissue, and cord blood for Spike protein 90 by Western blot and vaccine mRNA by PCR. All available delivery samples (maternal blood, 91 placental tissue, and cord blood) were negative for Spike protein by Western blot (Supp Figure   92 1, Supp Table 3) and did not have detectable levels of vaccine mRNA by PCR (Suppl Table 3).

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Together, this indicates that products of mRNA vaccination do not reach the fetus after 94 vaccination during pregnancy at readily detectable levels. 95 96 mRNA vaccination in pregnancy leads to a robust antibody response 97 Similar to prior studies 14,15,17 , we found that mRNA vaccination during pregnancy led to 98 an increase in anti-SARS-Cov-2 IgG following dose 1 (n=7, mean 388.6, SD 224.8 RFU) and an 99 even further robust increase after vaccination dose 2 (n=12, mean 3214, SD 1383 RFU). Anti-100 SARS-CoV-2 IgM (n=7, mean 53.3, SD 50.2 RFU) was detected in two maternal participants 101 following dose 1, but only 1 participant following dose 2 (n=12, mean 23.8, SD 17 RFU, Fig 1). 110 RFU). One participant received one mRNA vaccine dose 9 days prior to delivery, and both the 111 maternal and cord blood were negative for IgG at the time of delivery. Another participant 112 received two doses of mRNA vaccine (23 and 2 days) prior to delivery and maternal blood was 113 positive at 55 RFU (positive cutoff >50 RFU), however cord blood IgG was negative ( Figure 2A).

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We next evaluated the transplacental transfer of neutralizing antibody titers by a label-118 free surrogate neutralization assay (sVNT) from mother to cord blood. Maternal and cord blood 119 at delivery had robust neutralizing responses (maternal n=17, mean 220.2, range [0, 422]. Cord 120 blood n=16, mean 296.6, range [0, 485], Fig 2B). All mother-infant dyads with positive IgG 121 serology at delivery had detectable transplacental transfer of neutralizing antibodies with the 122 exception of one pair in which the mother was borderline IgG positive at delivery and cord blood 123 was negative, for which both maternal and cord blood were negative for neutralizing titers (Fig   124   2B). However, maternal and cord blood neutralizing titers were not significantly correlated 125 (p=0.361, Rs=-0.244, Fig 2B). Taken together, this indicates that maternal mRNA vaccination   Fig 2A), with one 133 infant still IgG positive at 12 weeks of age ( Fig 2C). The two infants that were IgG negative at 134 follow up were both born to mothers who received only one vaccine dose prior to delivery (6 and 135 9 days, respectively). One of these infants did not have paired maternal or cord blood available

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We assessed the relationship of anti-SARS-CoV-2 IgG levels to neutralizing antibody 154 levels. We found a strong correlation between IgG and neutralizing titers in maternal plasma at 155 delivery (Rs=0.744, p=0.0012) and infant follow up (Rs=0.738, p=0.046) timepoints, but no 156 significant association between IgG and neutralizing titers in cord blood (Rs=0.121, p=0.656, 157 Figure 3).

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We then evaluated the impact of timing of vaccination on maternal antibody levels at 159 delivery. We found no statistically significant correlation between maternal IgG levels at delivery

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To assess facilitated antibody transfer, we evaluated cord-to-maternal antibody IgG and 170 neutralization titer ratios by time since vaccination and gestational age. We found that IgG ratios 171 were highly correlated with both time since first maternal vaccination dose and gestational age

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We found that the timing of immunization during pregnancy is important to ensure trans-

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Consistent with observations in non-pregnant adults, we found that IgG levels in mothers 255 at delivery, and at infant follow-up were highly correlated with neutralizing titers 28 . However, 256 cord blood IgG levels did not correlate with neutralizing titers. Moreover, IgG cord-to-maternal 257 ratios, which represent a proxy of maternal to fetal antibody transfer, were highly correlated with 258 timing of vaccination (gestational age and days since the first dose), but cord-to-maternal 259 neutralizing titer ratios were not significantly associated with time since vaccination nor

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We thank all the mothers and infants that participated in this study. We thank Kenneth Scott,