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No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination

Alice Lu-Culligan, Alexandra Tabachnikova, Maria Tokuyama, Hannah J. Lee, Carolina Lucas, Valter Silva Monteiro, M. Catherine Muenker, Subhasis Mohanty, Jiefang Huang, Insoo Kang, Charles Dela Cruz, Shelli Farhadian, Melissa Campbell, Inci Yildirim, Albert C. Shaw, View ORCID ProfileAlbert I. Ko, Saad B. Omer, View ORCID ProfileAkiko Iwasaki
doi: https://doi.org/10.1101/2021.12.07.471539
Alice Lu-Culligan
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
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Alexandra Tabachnikova
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
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Maria Tokuyama
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
2Department of Microbiology and Immunology, The University of British Columbia, Vancouver, CA
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Hannah J. Lee
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
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Carolina Lucas
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
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Valter Silva Monteiro
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
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M. Catherine Muenker
3Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
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Subhasis Mohanty
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
4Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
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Jiefang Huang
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
4Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
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Insoo Kang
5Section of Rheumatology, Allergy and Immunology, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
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Charles Dela Cruz
6Section of Pulmonary and Critical Care Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
7Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT, USA
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Shelli Farhadian
4Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
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Melissa Campbell
4Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
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Inci Yildirim
8Division of Pediatric Infectious Diseases, Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA
3Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
9Yale Institute for Global Health, Yale University, New Haven, CT, USA
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Albert C. Shaw
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
4Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
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Albert I. Ko
3Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
4Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
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  • ORCID record for Albert I. Ko
Saad B. Omer
3Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
4Section of Infectious Diseases, Department of Medicine, Yale School of Medicine, New Haven, CT, USA
9Yale Institute for Global Health, Yale University, New Haven, CT, USA
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Akiko Iwasaki
1Department of Immunobiology, Yale School of Medicine, New Haven, CT, USA
3Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA
10Department of Molecular, Cellular and Developmental Biology, New Haven, CT, USA
11Howard Hughes Medical Institute, Chevy Chase, MD, USA
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  • ORCID record for Akiko Iwasaki
  • For correspondence: akiko.iwasaki@yale.edu
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Abstract

The impact of coronavirus disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated two of the most widely propagated claims to determine 1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities, and 2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.5 did not lead to differences in fetal size by crown-rump length or weight at term, nor did we observe any gross birth defects. In contrast, injection of the TLR3 agonist and double-stranded RNA mimic polyinosinic-polycytidylic acid, or poly(I:C), impacted growth in utero leading to reduced fetal size. No overt maternal illness following either vaccination or poly(I:C) exposure was observed. We also found that term fetuses from vaccinated murine pregnancies exhibit high circulating levels of anti-Spike and anti-RBD antibodies to SARS-CoV-2 consistent with maternal antibody status, indicating transplacental transfer. Finally, we did not detect increased levels of circulating anti-syncytin-1 antibodies in a cohort of COVID-19 vaccinated adults compared to unvaccinated adults by ELISA. Our findings contradict popular claims associating COVID-19 mRNA vaccination with infertility and adverse neonatal outcomes.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 08, 2021.
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No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination
Alice Lu-Culligan, Alexandra Tabachnikova, Maria Tokuyama, Hannah J. Lee, Carolina Lucas, Valter Silva Monteiro, M. Catherine Muenker, Subhasis Mohanty, Jiefang Huang, Insoo Kang, Charles Dela Cruz, Shelli Farhadian, Melissa Campbell, Inci Yildirim, Albert C. Shaw, Albert I. Ko, Saad B. Omer, Akiko Iwasaki
bioRxiv 2021.12.07.471539; doi: https://doi.org/10.1101/2021.12.07.471539
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No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination
Alice Lu-Culligan, Alexandra Tabachnikova, Maria Tokuyama, Hannah J. Lee, Carolina Lucas, Valter Silva Monteiro, M. Catherine Muenker, Subhasis Mohanty, Jiefang Huang, Insoo Kang, Charles Dela Cruz, Shelli Farhadian, Melissa Campbell, Inci Yildirim, Albert C. Shaw, Albert I. Ko, Saad B. Omer, Akiko Iwasaki
bioRxiv 2021.12.07.471539; doi: https://doi.org/10.1101/2021.12.07.471539

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