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[Preprint]. 2021 Dec 15:rs.3.rs-1150427.
doi: 10.21203/rs.3.rs-1150427/v1.

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

Mary Prahl  1 , Yarden Golan  2 , Arianna G Cassidy  3 , Yusuke Matsui  4 , Lin Li  3 , Bonny Alvarenga  5 , Hao Chen  6 , Unurzul Jigmeddagva  3 , Christine Y Lin  3 , Veronica J Gonzalez  3 , Megan A Chidboy  3 , Lakshmi Warrier  5 , Sirirak Buarpung  3 , Amy P Murtha  3 , Valerie J Flaherman  1 , Warner C Greene  4 , Alan H B Wu  7 , Kara L Lynch  7 , Jayant Rajan  5 , Stephanie L Gaw  3
Affiliations

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

Mary Prahl et al. Res Sq. .

Update in

Abstract

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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Figures

Figure 1.
Figure 1.. Anti-SARS-CoV-2 IgG and IgM antibody responses following vaccination
A. Maternal plasma anti-SARS-CoV-2 IgG antibody relative fluorescence units (RFU) levels prior to vaccination (n=4), 3–4 weeks post-dose 1 (n=7), and 4–8 weeks post-dose 2 (n=12). B. Maternal plasma anti-SARS-CoV-2 IgM (RFU) levels prior to vaccination (n=4), 3–4 weeks post-dose 1 (n=7), and 4–8 weeks post-dose 2 (n=12). Wilcoxon rank-sum testing. Data represent median ± quartiles, two-sided p values were calculated for all test statistics.
Figure 2.
Figure 2.. Paired maternal, cord, and infant IgG and neutralization antibodies
A. Paired maternal plasma at delivery (n=19), cord plasma (n=17), and infant follow-up (n=10) by anti-SARS-CoV-2 IgG antibody relative fluorescence units (RFU), (Spearman’s rank correlation, dotted line indicates positive cutoff value of 50 RFU). B. Paired maternal plasma at delivery (n=17), cord plasma (n=16), and infant follow-up (n=8) by SARS-CoV-2 label-free surrogate neutralization assay (sVNT), (Spearman’s rank correlation, dotted line indicates positive cutoff value of 25). C. Paired cord plasma (n=9) and infant follow-up plasma (n=11) anti-SARS-CoV-2 IgG by weeks of life. D. Paired cord plasma (n=7) and infant follow-up plasma (n=8) label-free surrogate neutralization assay (sVNT) by weeks of life. E. Paired maternal plasma at delivery (n=5), cord plasma (n=5), and paired maternal follow-up (n=5) and infant follow-up plasma (n=5) anti-SARS-CoV-2 IgG. Two-sided p values were calculated for all test statistics.
Figure 3.
Figure 3.. Neutralization to IgG antibody correlation
A. Maternal plasma at delivery (n=17) B. Cord plasma (n=16) C. Infant follow-up plasma (n=8) SARS-CoV-2 label-free surrogate neutralization assay (sVNT) by anti-SARS-CoV-2 IgG correlation (Spearman’s rank correlation). Two-sided p values were calculated for all test statistics.
Figure 4.
Figure 4.. Maternal delivery and Cord-to-maternal antibody transfer ratios timing
A. Maternal delivery anti-SARS-CoV-2 IgG antibody transfer ratio by days since vaccine dose 1 (n=19, dashed line indicates positive cutoff >50 RFU) B. Maternal delivery anti-SARS-CoV-2 IgG antibody transfer ratio by gestational age at vaccine dose 1 (n=19, dashed line indicates positive cutoff >50 RFU) C. Maternal delivery SARS-CoV-2 label-free surrogate neutralization assay (sVNT) antibody transfer ratio by days since vaccine dose 1 (n=17, dashed line indicates positive cutoff >25). D. Maternal delivery SARS-CoV-2 label-free surrogate neutralization assay (sVNT) antibody transfer ratio by gestational age at vaccine dose 1 (n=17, dashed line indicates positive cutoff >25) E. Cord-to-maternal anti-SARS-CoV-2 IgG antibody transfer ratio by days since vaccine dose 1 (n=15) F. Cord-to-maternal anti-SARS-CoV-2 IgG antibody transfer ratio by gestational age at vaccine dose 1 (n=15) G. Cord-to-maternal SARS-CoV-2 label-free surrogate neutralization assay (sVNT) antibody transfer ratio by days since vaccine dose 1 (n=15). H. Cord-to-maternal SARS-CoV-2 label-free surrogate neutralization assay (sVNT) antibody transfer ratio by gestational age at vaccine dose 1 (n=15). Two-sided p values were calculated for all test statistics.
Figure 5.
Figure 5.. PhIP-seq/VirScan paired maternal and cord SARS-CoV-2 Spike protein epitope binding
A. Heatmap displaying results of significant enriched (p<0.001) linear SARS-CoV-2 Spike protein epitope binding from 15 paired mother-infant dyads in maternal plasma at delivery and cord plasma by vaccine type and time since vaccine dose 1. Areas of high cumulative epitope binding designated by regions 1–4. B. Cumulative fold enrichment of mothers and infants linear SARS-CoV-2 Spike protein epitope binding.
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References

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