key: cord-1046950-kdqx9oqx
authors: Rottenstreich, Amihai; Zarbiv, Gila; Oiknine-Djian, Esther; Zigron, Roy; Wolf, Dana G; Porat, Shay
title: Efficient maternofetal transplacental transfer of anti- SARS-CoV-2 spike antibodies after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination
date: 2021-04-03
journal: Clin Infect Dis
DOI: 10.1093/cid/ciab266
sha: 1e17a381248ea2ba0ebb816480c1057d5e5ece3d
doc_id: 1046950
cord_uid: kdqx9oqx

Maternal and cord blood sera were collected from 20 parturients who received the BNT162b2 vaccine. All women and infants were positive for anti S- and anti-RBD-specific IgG. Cord blood antibody concentrations were correlated to maternal levels and to time since vaccination. Antenatal SARS-CoV-2 vaccination may provide maternal and neonatal protection.

M a n u s c r i p t

The rapidly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has afflicted over 113 million individuals resulting in over 2.5 million deaths, since it was declared a pandemic by the World Health Organization on March 2020. The pressing need for effective tools to combat Coronavirus Disease 19 (COVID-19) has led to the accelerated development and recent approval of several targeted vaccines including two novel mRNAbased vaccines [1, 2] . A mass vaccination campaign using the BNT162b2 (Pfizer/BioNTech) mRNA vaccine has commenced in Israel in December 2020.

Pregnant women are at higher risk for COVID-19 related illness [3] [4] [5] [6] [7] . In addition, recent data show that severe SARS-CoV-2 infection is more common among infants as compared to older children [7, 8] Nevertheless, as pregnant women were excluded from the pivotal trials evaluating the aforementioned vaccines [1, 2] , their safety and efficacy in the setting of pregnancy remain unknown.

Despite these uncertainties and given the risk for severe disease course, the Center for Disease Control and Prevention (CDC), the world Health Organization (WHO), and other agencies support offering pregnant women to receive the SARS-CoV-2 vaccine following shared decision making [9] [10] [11] [12] . Due to the paucity of literature and the high clinical relevance, we aimed to investigate the maternal serologic response after SARS-CoV-2 vaccination during pregnancy and its related subsequent transplacental antibody transfer.

A prospective study following women admitted for delivery was performed in 

Following delivery, maternal and cord blood sera were collected for antibody measurement.

Spike protein (S) (Liaison SARS-CoV-2 S1/S2 IgG, DiaSorin, Saluggia, Italy) and receptor binding domain (RBD)-specific (Architect SARS-CoV-2 IgG II Quant assay, Abbott Diagnostics, Chicago, USA), IgG levels were evaluated in maternal and cord blood sera.

Maternal and cord blood sera were also tested for SARS-CoV-2 IgM (Liaison, DiaSorin, Saluggia, Italy).

Patient characteristics are described as proportions for categorical variables and medians and interquartile range (IQR) for continuous variables without a normal distribution. Antibody levels and placental transfer ratios are expressed as medians and IQR. Correlations were reported using the Spearman's test with the correspondent  s and P values. The data were analyzed using Software Package for Statistics and Simulation (IBM SPSS version 24, IBM Corp, Armonk, NY).

During the study period, 20 parturients who received two doses of SARS-CoV-2 BNT162b2 mRNA vaccine were approached and agreed to participate. Currently, there is lack of data regarding SARS-CoV-2 vaccination among pregnant women in terms of safety and efficacy. In addition, the degree of transplacental passive immunity induced by maternal SARS-CoV-2 vaccination is unestablished. In this regard, studies among pregnant women with SARS-CoV-2 infection reported conflicting results [13, 14] , with some suggesting compromised transplacental transfer of naturally acquired antibodies [14] , questioning the potential role of vaccination during pregnancy to confer neonatal protection against COVID-19.

Neonatal protection from infections is primarily dependent on maternally-derived, transplacentally acquired antibodies. We demonstrated an efficient placental transfer of IgG antibodies following maternal SARS-CoV-2 vaccination, and a positive correlation between maternal and cord blood antibody concentrations. Nevertheless, while neonatal antibody levels were satisfactory, placental transfer ratios were relatively lower as compared to prior studies of vaccine-elicited antibodies to influenza, pertussis, measles, rubella and hepatitis B, in which transfer ratios ranging from 0.8 to 1.7 have been reported [15, 16] . This concurs with a recent study among pregnant women with COVID-19 which also demonstrated diminished transplacental transfer of anti-SARS-CoV-2 IgG [9] . The mechanisms underlying this finding should be further investigated.

While the current study findings are promising, there are several questions which remain unanswered. First, the optimal timing for maternal vaccination is still unclear. In the current study, maternal and neonatal antibody levels were directly correlated to the time lapsed from vaccination, which is consistent with studies of respiratory syncytial virus vaccine given during pregnancy [17] . However, as all women in the current cohort were vaccinated during the third-trimester, whether earlier vaccination would result in similar antibody concentrations requires further evaluation. In this regard, it is worth noting that for the Tdap vaccine, the optimal timing to maximize the maternal antibody response and passive This study has several caveats, including its small sample size and single-site nature. In addition, the association between gestational age at delivery with transplacental transfer requires further investigation. Moreover, as previously stated, the effect of SARS-CoV-2 vaccination at different times throughout gestation remains to be explored.

Our findings demonstrate that antenatal SARS-CoV-2 vaccination induces an adequate maternal serologic response and has the potential to provide neonatal protection through transplacental transfer of vaccine-stimulated maternally-derived antibodies. These encouraging results have important implications for maternal care and the development of appropriate vaccination strategies. Further studies will be needed to better delineate the safety and efficacy of the different maternal SARS-CoV-2 vaccines available and better define transplacental antibody dynamics at earlier gestational ages.

A c c e p t e d M a n u s c r i p t

Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine

Efficacy and safety of the mRNA-1273 SARSCoV-2 vaccine

Update: characteristics of symptomatic women of reproductive age with laboratory-confirmed SARS-CoV-2 infection by pregnancy status -United States

Clinical characteristics and outcomes of hospitalized women giving birth with and without COVID-19

Higher SARS-CoV-2 Infection Rate in Pregnant Patients

Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19)

CDC COVID-19 Response Pregnancy and Infant Linked Outcomes Team; COVID-19 Pregnancy and Infant Linked Outcomes Team (PILOT)

COVID-NET Surveillance Team. Hospitalization rates and characteristics of children aged <18 years hospitalized with confirmed COVID-19-COVID-NET, 14 states

COVID-19 (coronavirus disease): people with certain medical conditions

The coronavirus disease 2019 vaccine in pregnancy: risks, benefits, and recommendations

The American College of Obstetricians and Gynecologists. Vaccinating pregnant and lactating patients against COVID-19

Society for Maternal-Fetal Medicine (SMFM) Statement: SARS-Co-V-2 Vaccination in pregnancy

Assessment of maternal and neonatal cord blood SARS-CoV-2 antibodies and placental transfer ratios

Assessment of maternal and neonatal SARS-CoV-2 viral load, transplacental antibody transfer, and placental pathology in pregnancies during the COVID-19 pandemic

Efficiency of placental transfer of vaccine-elicited antibodies relative to prenatal Tdap vaccination status

Dr Rottenstreich had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.Concept and design: Porat, Rottenstreich, Wolf. Acquisition, analysis, or interpretation of data: All authors.Drafting of the manuscript: Rottenstreich, Zigron, Zarbiv, Porat, Wolf.Laboratory analyses: Oiknine-Djian, Wolf.Statistical analysis: Rottenstreich.All authors read and approved the final manuscript.

We thank Dr. Doron Kabiri, Dr. Shlomi Yahalomi, Prof. Yosef Ezra and Dr. Roy Alter for their assistance in patients' enrollment. We also thank Rimma Barsuk and Yulia Yachnin for their technical assistance..

The authors declare that they have no conflicts of interest.

No external funding was used for this study. A c c e p t e d M a n u s c r i p t