Ofer Beharier1, Romina Plitman Mayo2, Tal Raz3, Kira Nahum Sacks4, Letizia Schreiber5, Yael Suissa-Cohen1, Rony Chen6, Rachel Gomez-Tolub6, Eran Hadar6, Rinat Gabbay-Benziv7, Yuval Jaffe Moshkovich7, Tal Biron-Shental8, Gil Shechter-Maor8, Sivan Farladansky-Gershnabel8, Hen Yitzhak Sela9, Hedi Benyamini-Raischer10, Nitzan D Sela10, Debra Goldman-Wohl1, Ziv Shulman11, Ariel Many12, Haim Barr13, Simcha Yagel1, Michal Neeman2, Michal Kovo4. 1. Department of Obstetrics and Gynecology, Hadassah Hebrew University Medical Center, Jerusalem, Israel. 2. Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel. 3. Koret School of Veterinary Medicine, Hebrew University of Jerusalem, Rehovot, Israel. 4. Department of Obstetrics and Gynecology, Wolfson Medical Center, Holon, Israel. 5. Department of Pathology, Wolfson Medical Center, Holon, Israel. 6. Helen Schneider Hospital for Women, Rabin Medical Center, Petach Tikva, Israel. 7. Department of Obstetrics and Gynecology, The Hillel Yaffe Medical Center, Hadera, Israel. 8. Department of Obstetrics and Gynecology, Meir Medical Center, Kfar Saba, Israel. 9. Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel. 10. Department of Obstetrics and Gynecology, HaEmek Medical Center, Afula, Israel. 11. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. 12. Lis Hospital for Women, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 13. The Nancy and Stephen Grand Israel National Center for Personalized Medicin, Weizmann Institute of Science, Rehovot, Israel.
Abstract
BACKGROUND: The significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection. METHODS: A multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to three study groups: vaccinated (n=86); PCR confirmed SARS-CoV-2 infected during pregnancy (n=65), and unvaccinated non-infected controls (n=62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD and N). RESULTS: BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (Anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer rate was significantly lower for third-trimester as compared to second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group. CONCLUSIONS: Antenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy. FUNDING: Israel Science Foundation KillCorona grant 3777/19 (to MN, MK, SY, AM). Research grant from the Weizmann Institute Fondazione Henry Krenter (to MN).
BACKGROUND: The significant risks posed to mothers and fetuses by COVID-19 in pregnancy have sparked a worldwide debate surrounding the pros and cons of antenatal SARS-CoV-2 inoculation, as we lack sufficient evidence regarding vaccine effectiveness in pregnant women and their offspring. We aimed to provide substantial evidence for the effect of BNT162b2 mRNA vaccine versus native infection on maternal humoral, as well as transplacentally acquired fetal immune response, potentially providing newborn protection. METHODS: A multicenter study where parturients presenting for delivery were recruited at 8 medical centers across Israel and assigned to three study groups: vaccinated (n=86); PCR confirmed SARS-CoV-2 infected during pregnancy (n=65), and unvaccinated non-infected controls (n=62). Maternal and fetal blood samples were collected from parturients prior to delivery and from the umbilical cord following delivery, respectively. Sera IgG and IgM titers were measured using Milliplex MAP SARS-CoV-2 Antigen Panel (for S1, S2, RBD and N). RESULTS: BNT162b2 mRNA vaccine elicits strong maternal humoral IgG response (Anti-S and RBD) that crosses the placenta barrier and approaches maternal titers in the fetus within 15 days following the first dose. Maternal to neonatal anti-COVID-19 antibodies ratio did not differ when comparing sensitization (vaccine vs. infection). IgG transfer rate was significantly lower for third-trimester as compared to second trimester infection. Lastly, fetal IgM response was detected in 5 neonates, all in the infected group. CONCLUSIONS: Antenatal BNT162b2 mRNA vaccination induces a robust maternal humoral response that effectively transfers to the fetus, supporting the role of vaccination during pregnancy. FUNDING: Israel Science Foundation KillCorona grant 3777/19 (to MN, MK, SY, AM). Research grant from the Weizmann Institute Fondazione Henry Krenter (to MN).
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