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

Caroline Atyeo, Elizabeth A. DeRiso, Christine Davis, Evan A. Bordt, Rose M. DeGuzman, Lydia L. Shook, Lael M. Yonker, Alessio Fasano, Babatunde Akinwunmi, Douglas A. Lauffenburger, Michal A. Elovitz, Kathryn J. Gray, View ORCID ProfileAndrea G. Edlow, Galit Alter
doi: https://doi.org/10.1101/2021.04.04.438404
Caroline Atyeo
1Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
2PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, MA 02115, USA
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Elizabeth A. DeRiso
1Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
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Christine Davis
3Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Evan A. Bordt
4Department of Pediatrics, Lurie Center for Autism, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
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Rose M. DeGuzman
5Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
6Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
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Lydia L. Shook
5Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
6Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
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Lael M. Yonker
7Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA, USA
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Alessio Fasano
7Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA, USA
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Babatunde Akinwunmi
8Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA
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Douglas A. Lauffenburger
3Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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Michal A. Elovitz
9Maternal and Child Health Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
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Kathryn J. Gray
8Department of Obstetrics and Gynecology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02115, USA
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  • For correspondence: KGRAY6@BWH.HARVARD.EDU AEDLOW@MGH.HARVARD.EDU GALTER@mgh.harvard.edu
Andrea G. Edlow
5Department of Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
6Vincent Center for Reproductive Biology, Massachusetts General Hospital, Boston, MA 02114, USA
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  • ORCID record for Andrea G. Edlow
  • For correspondence: KGRAY6@BWH.HARVARD.EDU AEDLOW@MGH.HARVARD.EDU GALTER@mgh.harvard.edu
Galit Alter
1Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
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  • For correspondence: KGRAY6@BWH.HARVARD.EDU AEDLOW@MGH.HARVARD.EDU GALTER@mgh.harvard.edu
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Abstract

Significant immunological changes occur throughout pregnancy to tolerize the mother and allow growth of the fetal graft. However, additional local and systemic immunological adaptations also occur, allowing the maternal immune system to continue to protect the dyad against foreign invaders both during pregnancy and after birth through lactation. This fine balance of tolerance and immunity, along with physiological and hormonal changes, contribute to increased susceptibility to particular infections in pregnancy, including more severe COVID-19 disease. Whether these changes also make pregnant women less responsive to vaccination or induce altered immune responses to vaccination remains incompletely understood. To holistically define potential changes in vaccine response during pregnancy and lactation, we deeply profiled the humoral vaccine response in a group of pregnant and lactating women and non-pregnant age-matched controls. Vaccine-specific titers were comparable, albeit slightly lower, between pregnant and lactating women, compared to non-pregnant controls. Among pregnant women, we found higher antibody titers and functions in those vaccinated with the Moderna vaccine. FcR-binding and antibody effector functions were induced with delayed kinetics in both pregnant and lactating women compared to non-pregnant women. Antibody boosting resulted in high FcR-binding titers in breastmilk. These data point to an immune resistance to generate highly inflammatory antibodies during pregnancy and lactation, and a critical need to follow prime/boost timelines in this vulnerable population to ensure full immunity is attained.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • One Sentence Summary: While pregnant and lactating women mount comparable final antibody titers to non-pregnant in response to the mRNA COVID-19 vaccines, pregnant and lactating women have a longer window of vulnerability after the first dose, develop different functional and FcR-binding profiles compared to non-pregnant, and exhibit distinct responses to Moderna and Pfizer/BioNTech vaccines.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted April 05, 2021.
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COVID-19 mRNA vaccines drive differential Fc-functional profiles in pregnant, lactating, and non-pregnant women
Caroline Atyeo, Elizabeth A. DeRiso, Christine Davis, Evan A. Bordt, Rose M. DeGuzman, Lydia L. Shook, Lael M. Yonker, Alessio Fasano, Babatunde Akinwunmi, Douglas A. Lauffenburger, Michal A. Elovitz, Kathryn J. Gray, Andrea G. Edlow, Galit Alter
bioRxiv 2021.04.04.438404; doi: https://doi.org/10.1101/2021.04.04.438404
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COVID-19 mRNA vaccines drive differential Fc-functional profiles in pregnant, lactating, and non-pregnant women
Caroline Atyeo, Elizabeth A. DeRiso, Christine Davis, Evan A. Bordt, Rose M. DeGuzman, Lydia L. Shook, Lael M. Yonker, Alessio Fasano, Babatunde Akinwunmi, Douglas A. Lauffenburger, Michal A. Elovitz, Kathryn J. Gray, Andrea G. Edlow, Galit Alter
bioRxiv 2021.04.04.438404; doi: https://doi.org/10.1101/2021.04.04.438404

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