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

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. Here, we evaluate 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 late pregnancy. We find no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery. However, we find time-dependent efficient transfer of IgG and neutralizing antibodies to the neonate that persists during early infancy. Additionally, using phage immunoprecipitation sequencing, we find a vaccine-specific signature of SARS-CoV-2 Spike protein epitope binding that is transplacentally transferred during pregnancy. Timing of vaccination during pregnancy is critical to ensure transplacental transfer of protective antibodies during early infancy.

Fig. 1. Anti-SARS-CoV-2 IgG and IgM antibody responses following vaccination.

A Maternal plasma anti-SARS-CoV-2 RBD/N 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 RBD/N 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. Source data are provided as a source data file.

Fig. 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 = 11) by anti-SARS-CoV-2 RBD/N 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 RBD/N 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 RBD/N IgG. Two-sided p values were calculated for all test statistics. Source data are provided as a source data file.

Fig. 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 RBD/N IgG relative fluorescence units (RFU) correlation (Spearman’s rank correlation). Two-sided p values were calculated for all test statistics. Source data are provided as a source data file.

Fig. 4. Maternal delivery and Cord-to-maternal antibody transfer ratios timing.

A Maternal delivery anti-SARS-CoV-2 RBD/N IgM antibody level by days since vaccine dose 1 (n = 17, dashed line indicates positive cutoff >50 relative fluorescence units (RFU)). B Maternal delivery anti-SARS-CoV-2 RBD/N IgG antibody level by days since vaccine dose 1 (n = 17, dashed line indicates positive cutoff >50 RFU). C Maternal delivery anti-SARS-CoV-2 RBD/N IgG antibody level by gestational age at vaccine dose 1 (n = 17, dashed line indicates positive cutoff >50 RFU). D Maternal delivery SARS-CoV-2 label-free surrogate neutralization assay (sVNT) antibody titer days since vaccine dose 1 (n = 16, dashed line indicates positive cutoff >25). E Maternal delivery SARS-CoV-2 label-free surrogate neutralization assay (sVNT) antibody titer by gestational age at vaccine dose 1 (n = 16, dashed line indicates positive cutoff >25). A–E Samples with vaccine dose 1 < 30 days prior to delivery (indicated by half circles) excluded from presented analysis. F Cord-to-maternal anti-SARS-CoV-2 RBD/N IgG antibody transfer ratio by cord-to-maternal label-free surrogate neutralization assay (sVNT) antibody transfer ratio (n = 15). G Cord-to-maternal anti-SARS-CoV-2 RBD/N IgG antibody transfer ratio by days since vaccine dose 1 (n = 15). H Cord-to-maternal anti-SARS-CoV-2 RBD/N IgG antibody transfer ratio by gestational age at vaccine dose 1 (n = 15). I Cord-to-maternal SARS-CoV-2 label-free surrogate neutralization assay (sVNT) antibody transfer ratio by days since vaccine dose 1 (n = 15). J Cord-to-maternal SARS-CoV-2 label-free surrogate neutralization assay (sVNT) antibody transfer ratio by gestational age at vaccine dose 1 (n = 15). Spearman’s rank correlation. Two-sided p values were calculated for all test statistics. Source data are provided as a source data file.

Fig. 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. Counts per 100,000 reads for all peptides were modeled against the distribution of rp100k in healthy control samples modeled as normally distributed. One-sided calculated p values were corrected for multiple hypothesis using the Benjamini–Hochberg method. Any peptide with a corrected p value of <0.001 was considered significantly enriched over the healthy background. NTD = N-terminal domain, RBD = receptor binding domain, S1 = Spike 1 subunit, S2 = Spike 2 subunit, TM = Transmembrane. Source data are provided as a source data file link.