Newborns’ Passive Humoral SARS-CoV-2 Immunity Following Heterologous Vaccination Of The Mother During Pregnancy

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OBJECTIVE:

Vaccination during the SARS-CoV-2 pandemic is important, especially to protect pregnant women and the unborn. 

In 2021, the messenger RNA (mRNA)-based vaccines BNT162b2 (BioNTech/Pfizer) and mRNA-1273 (Moderna), and the vector-based vaccine AZD1222 (AstraZeneca) was approved for use in Germany.1 Vaccination for pregnant women was considered after weighing the individual benefits and risks of the vaccines without preference for a vaccine type.1 After national guidelines discouraged the use of AZD1222 in those under 60 years of age,1 mRNA-based boost vaccination was recommended. 

In this study, we intend to evaluate antibody kinetics following heterologous vaccination in pregnant women in comparison to their newborns as well as to a healthy nonpregnant control group.

STUDY DESIGN:

We recruited 3 pregnant participants (gestational age at primary vaccination between 21 and 28 weeks) and 25 nonpregnant control participants at the Jena University Hospital. They were observed after prime vaccination with AZD1222 and boost vaccination 12 weeks thereafter with either BNT162b2 or mRNA-1273. Ethical approval was obtained for the same (Jena University Hospital ethics commission ref.: 2021-2078). The anti-Spike immunoglobulin G (IgG) antibody levels were determined in the serial serum samples (before and 1, 2, 3, 4, 5, 8, and 16 weeks after prime vaccination) and, if available, in the maternal and cord serum at the time of birth using the LIAISON SARS-CoV-2 TrimericS IgG assay on the Liaison XL chemiluminescence analyzer (DiaSorin, Saluggia, Italy), according to the manufacturer’s instructions. The neutralization capacity was tested in a neutralization assay using Vero-76 cells and a SARS-CoV-2 strain isolated from a respiratory specimen (SARS-CoV-2/hu/Germany/Jenavi005588/2020), utilizing WST-1 (CELLPRO-RO, Roche, Basel, Switzerland) to quantify cell viability after infection. The neutralization titer was defined as the inverted maximal dilution at which 50% of the cytopathic effect caused by the virus was neutralized (ID50). 

For the pregnant participants, the recombine SARS-CoV-2 IgG immunoblot (Mikrogen, Neuried, Germany) was performed 16 weeks after the initial vaccination to rule out interfering infection by measuring the nucleocapsid IgG antibodies.

RESULTS:

The SARS-CoV-2 Spike IgG antibodies were detected for all the study participants (Figure), with ID50 (inhibitory serum dilution showing a 50% neutralization of the viral effects on cell viability) and neutralization titers 160 in maternal and cord serum samples. 

The immunoblot showed distinct signals in both the receptor-binding domain and the Spike subunit 1 IgG for all the pregnant participants but showed no signal for nucleocapsid antibodies. Severe adverse events requiring hospitalization were not reported during the observational period, and all the 3 pregnant participants delivered at term.

CONCLUSION:

Vaccine-induced SARS-CoV-2 antibodies were already described after the mRNA-based COVID-19 vaccination of pregnant women equivalent to nonpregnant women,2 with a correlation of maternal and neonatal antibody levels.3,4 The noninferiority of heterologous vaccination when compared with homologous regimens was recently reported in nonpregnant women.5 

We detected vaccine-induced SARS-CoV-2 Spike IgG antibodies after vector-based prime vaccination in pregnancy, with an average increase of more than one log10 level after an mRNA-based boost. SARS-CoV-2 infection during pregnancy was ruled out because of negative nucleocapsid IgG results. The observed immune response in pregnant women showed no significant difference compared with nonpregnant controls 16 weeks after the initial vaccination (Mann-Whitney U test: P¼.514).

We found similar levels of anti-Spike IgG antibodies with a high neutralization capacity in the cord serum, indicating a strong passive humoral immunity in newborns.

ACKNOWLEDGMENTS

We would like to thank Kathrin Schulze for the excellent technical assistance.

Stefan Gloeckner, MD Franziska Hornung, MSc Institute of Medical Microbiology Jena University Hospital Am Klinikum 1, D-07747 Jena, Germany.

Yvonne Heimann, MSc Ekkehard Schleussner, MD Department of Obstetrics Jena University Hospital Jena, Germany.

Stefanie Deinhardt-Emmer, MD Bettina Loeffler, MD Institute of Medical Microbiology Jena University Hospital Jena, Germany.

Janine Zoellkau, MD Department of Obstetrics Jena University Hospital Jena, Germany.

The authors report no conflict of interest.

This study was funded with internal funds from the Jena University Hospital and the Center for Sepsis Control and Care.

1. Vygen-Bonnet S, Koch J, Bogdan C, et al. Beschluss der STIKO zur 4. Aktualisierung der COVID-19-Impfempfehlung und die dazugehörige wissenschaftliche Begründung. Epid Bull 2021;16:3–78. 

2. Gray KJ, Bordt EA, Atyeo C, et al. Coronavirus disease 2019 vaccine response in pregnant and lactating women: a cohort study. Am J Obstet Gynecol 2021;225:303.e1–17. 

3. Kubiak JM, Murphy EA, Yee J, et al. Severe acute respiratory syndrome coronavirus 2 serology levels in pregnant women and their neonates. Am J Obstet Gynecol 2021;225:73.e1–7. 

4. Mithal LB, Otero S, Shanes ED, Goldstein JA, Miller ES. Cord blood antibodies following maternal coronavirus disease 2019 vaccination during pregnancy. Am J Obstet Gynecol 2021;225:192–4. 

5. Liu X, Shaw RH, Stuart AS, et al. Safety and immunogenicity of heterologous versus homologous prime-boost schedules with an adenoviral vector and mRNA COVID-19 vaccine (Com-COV): a single-blind, randomized, non-inferiority trial. Lancet 2021;398: 856–69.

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