COVID-19 mRNA vaccines drive differential antibody Fc-functional profiles in pregnant, lactating, and nonpregnant women

Atyeo, Caroline; DeRiso, Elizabeth A.; Davis, Christine; Bordt, Evan A.; Guzman, Rose M. De; Shook, Lydia L.; Yonker, Lael M.; Fasano, Alessio; Akinwunmi, Babatunde; Lauffenburger, Douglas A.; Elovitz, Michal A.; Gray, Kathryn J.; Edlow, Andrea G.; Alter, Galit

doi:10.1126/scitranslmed.abi8631

“…We found that the timing of immunization during pregnancy is important to ensure transplacental transfer of protective antibodies to the neonate, and during critical windows of immune vulnerability during early infancy. Consistent with prior studies showing robust immune responses to mRNA vaccination 14,15,17 , we found high levels of IgG after two doses of mRNA vaccine. However, completion of the vaccination series well before delivery was important to ensure transfer of antibodies to the infant.…”

Section: Discussionsupporting

confidence: 91%

“…Similar to prior studies 14,15,17 , we found that mRNA vaccination during pregnancy led to an increase in anti-SARS-Cov-2 IgG following dose 1 (n=7, mean 388.6, SD 224.8 RFU) and an even further robust increase after vaccination dose 2 (n=12, mean 3214, SD 1383 RFU). Anti-SARS-CoV-2 IgM (n=7, mean 53.3, SD 50.2 RFU) was detected in two maternal participants following dose 1, but only 1 participant following dose 2 (n=12, mean 23.8, SD 17 RFU, Fig 1).…”

Section: Mrna Vaccination In Pregnancy Leads To a Robust Antibody Responsesupporting

confidence: 89%

“…During gestation there is facilitated transfer of maternally derived antibodies through the binding of the neonatal Fc receptor in the synctiotrophoblast layer 29 . Differences in glycosylation 30,31 , FcR/FcRn binding affinity 17,32 , preferential IgG subclass transfer 33,34 may be different in functional neutralizing antibodies as compared to total IgG antibody transfer.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Prahl

¹

,

Golan

²

,

Cassidy

³

et al. 2021

Preprint

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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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“…Further, our results showing a sustained anti-RBD antibody response in milk may have implications for the durability of vaccine-induced milk antibodies. Indeed, similar to SARS-CoV-2 infection and maternal vaccination against other respiratory pathogens ( 20 , 21 ), recent data demonstrate that in the days and weeks following maternal COVID-19 vaccination, a robust IgG-dominant milk antibody response is induced ( 22 – 25 ), although the longer-term durability of the milk-borne antibody response remains to be elucidated. Similarly, the mechanisms underlying the persistence or lack of specific antibodies in human milk are not well understood, but may be related to differences in the course of the infection, recurrent exposures and/or the migration of long-lived plasma cells from mucosal sites to the mammary gland ( 26 – 28 )…”

Section: Discussionmentioning

confidence: 99%

Milk From Women Diagnosed With COVID-19 Does Not Contain SARS-CoV-2 RNA but Has Persistent Levels of SARS-CoV-2-Specific IgA Antibodies

Pace

¹

,

Williams

²

,

Järvinen

³

et al. 2021

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BackgroundLimited data are available regarding the balance of risks and benefits from human milk and/or breastfeeding during and following maternal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).ObjectiveTo investigate whether SARS-CoV-2 can be detected in milk and on the breast after maternal coronavirus disease 2019 (COVID-19) diagnosis; and characterize concentrations of milk immunoglobulin (Ig) A specific to the SARS-CoV-2 spike glycoprotein receptor binding domain (RBD) during the 2 months after onset of symptoms or positive diagnostic test.MethodsUsing a longitudinal study design, we collected milk and breast skin swabs one to seven times from 64 lactating women with COVID-19 over a 2-month period, beginning as early as the week of diagnosis. Milk and breast swabs were analyzed for SARS-CoV-2 RNA, and milk was tested for anti-RBD IgA.ResultsSARS-CoV-2 was not detected in any milk sample or on 71% of breast swabs. Twenty-seven out of 29 (93%) breast swabs collected after breast washing tested negative for SARS-CoV-2. Detection of SARS-CoV-2 on the breast was associated with maternal coughing and other household COVID-19. Most (75%; 95% CI, 70-79%; n=316) milk samples contained anti-RBD IgA, and concentrations increased (P=.02) during the first two weeks following onset of COVID-19 symptoms or positive test. Milk-borne anti-RBD IgA persisted for at least two months in 77% of women.ConclusionMilk produced by women with COVID-19 does not contain SARS-CoV-2 and is likely a lasting source of passive immunity via anti-RBD IgA. These results support recommendations encouraging lactating women to continue breastfeeding during and after COVID-19 illness.

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“…During gestation there is facilitated transfer of maternally derived antibodies through the binding of the neonatal Fc receptor in the synctiotrophoblast layer 29 . Differences in glycosylation 30,31 , FcR/FcRn binding affinity 17,32 , preferential IgG subclass transfer 33,34 may be different in functional neutralizing antibodies as compared to total IgG antibody transfer.…”

Section: Discussionmentioning

confidence: 99%

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

Prahl

¹

,

Golan

²

,

Cassidy

³

et al. 2021

Preprint

View full text Add to dashboard Cite

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.

show abstract

COVID-19 mRNA vaccines drive differential antibody Fc-functional profiles in pregnant, lactating, and nonpregnant women

Abstract: Pregnant and lactating women develop distinct antibody Fc profiles in response to the mRNA-1273 and BNT162b2 vaccines compared to nonpregnant women.

Cited by 92 publications

References 60 publications

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

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

Milk From Women Diagnosed With COVID-19 Does Not Contain SARS-CoV-2 RNA but Has Persistent Levels of SARS-CoV-2-Specific IgA Antibodies

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

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