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Am J Obstet Gynecol ; 2022 Jul 19.
Article in English | MEDLINE | ID: covidwho-1935983


BACKGROUND: While emerging data during the SARS-CoV-2 pandemic have demonstrated robust mRNA vaccine-induced immunogenicity across populations, including pregnant and lactating individuals, the rapid waning of vaccine-induced immunity and the emergence of variants of concern motivated the use of mRNA vaccine booster doses. Whether all populations, including pregnant and lactating individuals, will mount a comparable response to a booster dose is not known. OBJECTIVE: We sought to profile the humoral immune response to a COVID-19 mRNA booster dose in a cohort of pregnant, lactating, and age-matched nonpregnant women. STUDY DESIGN: We characterized the antibody response against ancestral Spike and Omicron in a cohort of 31 pregnant, 12 lactating and 20 nonpregnant age-matched controls who received a BNT162b2 or mRNA-1273 booster dose after primary COVID-19 vaccination. We also examined the vaccine-induced antibody profiles of 15 maternal:cord dyads at delivery. RESULTS: Receipt of a booster dose during pregnancy resulted in increased IgG1 against Omicron Spike (post-primary vaccination vs post-booster, p = 0.03). Pregnant and lactating individuals exhibited equivalent Spike-specific total IgG1, IgM and IgA levels and neutralizing titers against Omicron compared to nonpregnant women. Subtle differences in Fc-receptor binding and antibody subclass profiles were observed in the immune response to a booster dose in pregnant compared to nonpregnant individuals. Analysis of maternal and cord antibody profiles at delivery demonstrated equivalent total Spike-specific IgG1 in maternal and cord blood, yet higher Spike-specific FcγR3a-binding antibodies in the cord relative to maternal blood (p = 0.002), consistent with preferential transfer of highly functional IgG. Spike-specific IgG1 levels in the cord were positively correlated with time elapsed since receipt of the booster dose (Spearman R 0.574, p = 0.035). CONCLUSIONS: These data suggest that receipt of a booster dose during pregnancy induces a robust Spike-specific humoral immune response, including against Omicron. If boosting occurs in the third trimester, higher Spike-specific cord IgG1 levels are achieved with greater time elapsed between receipt of the booster and delivery. Receipt of a booster dose has the potential to augment maternal and neonatal immunity.

Sci Transl Med ; 13(617): eabi8631, 2021 Oct 27.
Article in English | MEDLINE | ID: covidwho-1532951


Substantial immunological changes occur throughout pregnancy to render the mother immunologically tolerant to the fetus and allow fetal growth. However, additional local and systemic immunological adaptations also occur, allowing the maternal immune system to continue to protect the dyad against pathogens both during pregnancy and after birth through lactation. This fine balance of tolerance and immunity, along with physiological and hormonal changes, contributes to increased susceptibility to particular infections in pregnancy, including more severe coronavirus disease 2019 (COVID-19). Whether these changes also make pregnant women less responsive to vaccination or induce altered immune responses to vaccination remains incompletely understood. To define potential changes in vaccine response during pregnancy and lactation, we undertook deep sequencing of the humoral vaccine response in a group of pregnant and lactating women and nonpregnant age-matched controls. Vaccine-specific titers were comparable between pregnant women, lactating women, and nonpregnant controls. However, Fc receptor (FcR) binding and antibody effector functions were induced with delayed kinetics in both pregnant and lactating women compared with nonpregnant women after the first vaccine dose, which normalized after the second dose. Vaccine boosting resulted in high FcR-binding titers in breastmilk. These data suggest that pregnancy promotes resistance to generating proinflammatory antibodies and indicates that there is a critical need to follow prime-boost timelines in this vulnerable population to ensure full immunity is attained.

COVID-19 Vaccines , COVID-19 , Female , Humans , Lactation , Pregnancy , RNA, Messenger , SARS-CoV-2