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

• DOI: 10.1371/journal.pbio.3001506
• Publication Date: 2022-05-24T17:43:34Z
• Authors: Alice Lu-Culligan; Alexandra Tabachn...; Eddy Pérez-Then; Maria Tokuyama; Hannah J. Lee; Carolina Lucas; Valter Silva Mont...; Marija Miric; Vivian Brache; Leila Cochon; M. Catherine Muenker; Subhasis Mohanty; Jiefang Huang; Insoo Kang; Charles Dela Cruz; Shelli Farhadian; Melissa Campbell; Inci Yildirim; Albert C. Shaw; Shuangge Ma; Sten H. Vermund; Albert I. Ko; Saad B. Omer; Akiko Iwasaki
• Keywords: QH301-705.5; SARS-CoV-2; Placenta; Vaccination; COVID-19; Gene Products, env; Pregnancy Proteins; Antibodies, Viral; 3. Good health; Mice; 03 medical and health sciences; Fetus; 0302 clinical medicine; Short Reports; Pregnancy; Animals; Humans; Female; RNA, Messenger; Biology (General)

The impact of Coronavirus Disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated 2 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 these murine pregnancies vaccinated prior to the formation of the definitive placenta exhibit high circulating levels of anti-spike and anti-receptor-binding domain (anti-RBD) antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) consistent with maternal antibody status, indicating transplacental transfer in the later stages of pregnancy after early immunization. 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.