Women who are pregnant or breastfeeding should receive a COVID booster shot

In a recently published study medRxiv* Preprint servers, researchers assessed the effects of booster vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in lactating and pregnant women.

​​​​​​Study: COVID-19 booster dose antibody response in pregnant, lactating and non-pregnant women. ​​​​​​​Image credit: HTeam

background

Pregnant women are particularly vulnerable to coronavirus disease 2019 (COVID-19) as they are at higher risk of serious illness and adverse pregnancy outcomes such as stillbirth. Despite recommendations from the American College of Obstetricians and Gynecologists (ACOG) and the Centers for Disease Control and Prevention (CDC) for vaccination of pregnant women, their SARS-CoV-2 vaccination coverage is lower than that of the general adult population.

Previous reports showed that the SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccines induced robust immunogenicity in lactating and pregnant women. Nevertheless, thorough characterization of immune responses to primary COVID-19 vaccination in lactating and pregnant women revealed decreased fragment crystallizable (Fc) receptor binding and differences in subtype preference. These data indicate the delayed progression of a fully mature immune response against SARS-CoV-2 in the lactating and pregnant cohorts.

The introduction of booster doses of the COVID-19 mRNA vaccines was inspired by the rapid waning of vaccine-induced immunity and the emergence of worrisome SARS-CoV-2 variants (VOCs) such as Omicron. However, it is unclear whether all groups, particularly lactating and pregnant women, will respond in the same way to a booster dose.

About the study

In the current work, the researchers examined the humoral immunity elicited by the booster dose of SARS-CoV-2 mRNA vaccines in 63 subjects including lactating, pregnant and age-matched non-pregnant women. They studied the antibody response to the spike (S) proteins of the SARS-CoV-2 omicron and ancestral strains in a group of 12 lactating, 31 pregnant, and 20 non-pregnant age-matched volunteers harboring an mRNA-1273 or BNT162b2 Booster doses received after completion of primary COVID-19 vaccination. In addition, researchers analyzed transmission of vaccine-elicited antibodies in 15 pairs of umbilical cords at birth.

Eligible subjects were lactating, pregnant and non-pregnant women aged 18 to 45 years. In addition, all enrolled participants were vaccinated with a SARS-CoV-2 mRNA booster dose between August and December 2021. Participants were selected or self- referred by physicians from two tertiary care hospitals. Blood samples were taken from all volunteers four weeks after the booster vaccination and at delivery in pregnant women. In addition, umbilical cord and maternal blood was obtained during delivery from 15 women who gave birth during the research period.

The COVID-19 booster vaccine induces a similar spike-specific antibody response in pregnant, lactating, and non-pregnant individuals. A. Dot plots show the maximal anti-spike IgG1, IgA and IgM response in 5 pregnant subjects after receiving the second dose of a primary mRNA vaccine series (V2) and after the booster (V3). Lines connect samples from the same person. Significance was determined by a Wilcoxon signed rank test. The differences did not reach statistical significance. †p=0.06. B. Dot plots show anti-spike IgG1, IgA, and IgM levels in non-pregnant (NP), pregnant (P), and lactating (L) subjects. The horizontal line represents the median for each group. Significance was determined by a Kruskal-Wallis test. No comparisons were significant. C. Dot plots show FcR binding of anti-Spike antibodies in non-pregnant (NP), pregnant (P), and lactating (L) subjects. The horizontal line represents the median for each group. Significance was determined by a Kruskal-Wallis test. No comparisons were significant.

Results

The study results showed that the COVID-19 booster shot in pregnancy increased levels of Omicron S-specific immunoglobulin G1 (IgG1). Breastfeeding and pregnant women had SARS-CoV-2 omicron and ancestral S-specific total IgM, IgA, and IgG1 levels and neutralizing concentrations similar to non-pregnant women after the booster.

Multivariate analysis showed pregnancy-specific changes when changing antibody class and SARS-CoV-2-S-specific epitope coverage. The immune response to a booster dose in pregnant versus non-pregnant women showed subtle variations in Fc region-receptor binding and antibody subclass patterns. In particular, functional antibodies in non-pregnant women had greater specificity for the S2 domains and the N-terminal domain (NTD) of SARS-CoV-2, which may be important for the overall immune response to the S antigen. Surprisingly, the current results showed that breastfeeding women had a profile between non-pregnant and pregnant women.

Evaluation of cord and maternal antibody patterns at delivery after the third trimester booster dose showed similar total SARS-CoV-2-S-specific IgG1 in cord and maternal blood. In addition, S-specific Fc-γ resistance gene (R3a)-binding antibodies were higher in cord blood than in maternal blood, suggesting that high-efficiency IgG is preferentially transferred. The authors found that post-booster time was positively correlated with SARS-CoV-2 S-specific IgG1 concentrations in the spinal cord.

Transfer of Omicron Spike-specific antibodies to the umbilical cord after third-trimester vaccination. A. Dot plots show IgA and IgM versus spike in maternal (M) and cord blood (C). Lines connect matching maternal:cord dyads (n = 15). ***p<0.001, ****p<0.0001. B.C. Dot plots show the titer of IgG1 (B) and FcR binding (C) against Omicron Spike in maternal (M) and cord blood (C). Lines connect matching maternal:cord dyads (n = 15). Significance was determined by a Wilcoxon signed rank test followed by a Benjamini-Hochberg correction for multiple testing, *p<0.05. D. Scatterplot showing the correlation of log-transformed umbilical cord IgG1 levels against Omicron Spike versus days from maternal booster vaccination to delivery. The R value reflects a Spearman correlation.

Conclusions

The study results indicated that receiving a COVID-19 mRNA vaccine shot during pregnancy results in robust SARS-CoV-2-S-specific humoral immunity, including protection against Omicron VOC, in newborns and mothers who are infected correspond to non-pregnant women. In addition, the scientists indicated that with a last-trimester SARS-CoV-2 vaccine booster, S-specific umbilical cord IgG1 titers will be higher because antibody transmission is time-dependent.

Overall, the present work suggests that a COVID-19 booster dose in pregnant women could help boost neonatal and maternal immunity against SARS-CoV-2 infection. In addition, the authors mentioned that it is important to assess whether more booster doses or other vaccination platforms could increase epitope coverage in pregnancy and break SARS-CoV-2 receptor-binding domain (RBD) immunodominance.

*Important NOTE

medRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health behavior or treated as established information.