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. 2023 Jul 3:14:1211558.
doi: 10.3389/fimmu.2023.1211558. eCollection 2023.

COVID-19 vaccine induced poor neutralization titers for SARS-CoV-2 omicron variants in maternal and cord blood

Sakthivel Govindaraj  1   2 , Narayanaiah Cheedarla  1 , Suneethamma Cheedarla  1 , LesShon S Irby  3 , Andrew S Neish  1 , John D Roback  1 , Alicia K Smith  3 , Vijayakumar Velu  1   2
Affiliations

COVID-19 vaccine induced poor neutralization titers for SARS-CoV-2 omicron variants in maternal and cord blood

Sakthivel Govindaraj et al. Front Immunol. .

Abstract

Introduction: Maternally derived antibodies are crucial for neonatal immunity. Understanding the binding and cross-neutralization capacity of maternal and cord antibody responses to SARS-CoV-2 variants following COVID-19 vaccination in pregnancy can inform neonatal immunity.

Methods: Here we characterized the binding and neutralizing antibody profile at delivery in 24 pregnant individuals following two doses of Moderna mRNA-1273 or Pfizer BNT162b2 vaccination. We analyzed for SARS-CoV-2 multivariant cross-neutralizing antibody levels for wildtype Wuhan, Delta, Omicron BA1, BA2, and BA4/BA5 variants. In addition, we evaluated the transplacental antibody transfer by profiling maternal and umbilical cord blood.

Results: Our results reveal that the current COVID-19 vaccination induced significantly higher RBD-specific binding IgG titers in cord blood compared to maternal blood for both the Wuhan and Omicron BA1 strain. Interestingly, the binding IgG antibody levels for the Omicron BA1 strain were significantly lower when compared to the Wuhan strain in both maternal and cord blood. In contrast to the binding, the Omicron BA1, BA2, and BA4/5 specific neutralizing antibody levels were significantly lower compared to the Wuhan and Delta variants. It is interesting to note that the BA4/5 neutralizing capacity was not detected in either maternal or cord blood.

Discussion: Our data suggest that the initial series of COVID-19 mRNA vaccines were immunogenic in pregnant women, and vaccine-elicited binding antibodies were detectable in cord blood at significantly higher levels for the Wuhan and Delta variants but not for the Omicron variants. Interestingly, the vaccination did not induce neutralizing antibodies for Omicron variants. These results provide novel insight into the impact of vaccination on maternal humoral immune response and transplacental antibody transfer for SARS-CoV-2 variants and support the need for bivalent boosters as new variants emerge.

Keywords: COVID-19 vaccination; cord blood; omicron; pregnancy; variants of concern.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
COVID-19 mRNA vaccination in pregnant women lacks neutralizing antibodies to Omicron subvariants. (A) Experimental design—Recruitment of COVID-19-vaccinated pregnant women who had received a vaccination 14 days before delivery were enrolled in the study. (B) Box plot represents RBD-specific end point IgG titers for Wuhan (black) and Omicron BA1 (red) variants in both maternal and cord blood. (C) Box plot represents neutralizing antibody titers for maternal blood samples by luciferase-based pseudovirus neutralization assay for Wuhan (black), Delta (blue), Omicron BA1 (red), Omicron BA2 (orange), and Omicron BA4/BA5 (pink) variants. (D) Neutralizing antibody titers for cord blood samples for Wuhan (gray), Delta (light blue), Omicron BA1 (light red), Omicron BA2 (light orange), and Omicron BA4/BA5 (light pink) variants. (E) The percentage of detectable neutralization antibody titers in the maternal and cord blood for Wuhan, Delta, and Omicron subvariants. ns, Non Significant.
Figure 2
Figure 2
COVID-19 mRNA vaccines induced significantly lower neutralizing antibody transfer ratio. (A). Shows spike protein sequences comparing Delta, and Omicron BA1, BA2, and BA4/BA5 subvariants; mutations as compared with WA1/2020 spike protein are shown. (B). Displays the RBD-specific end point IgG titer transfer ratio for Wuhan and Omicron BA1 variant. The transplacental transfer ratio was calculated as cold blood IgG concentration divided by maternal IgG concentration. (C). The data shows the neutralization antibody transfer ratio for Wuhan, Delta, and Omicron variants, and the transfer ratio was poor in Omicron variants. ns, Non Significant.
Figure 3
Figure 3
A significant drop in the percentages of seropositive individuals with detectable neutralizing antibodies for the omicron BA1 variant. (A) Box plots represent similar detectable RBD-specific binding IgG antibodies in the maternal and cord blood for Wuhan and Omicron BA1 variants. (B) Box plot represents a significant drop in the detectable neutralizing antibodies level with the Omicron BA1 variant compared to wild type in the maternal and cord blood. ns, Non Significant.
Figure 4
Figure 4
Detectable binding and neutralizing antibody levels in maternal and cord blood correlated positively for all variants. (A) Wuhan RBD-specific binding IgG antibody levels correlation between maternal and cord blood. (B) Omicron RBD-specific binding antibody level correlation between maternal and cord blood. (C) Wuhan neutralizing antibody level correlation between maternal and cord blood. (D) Delta-specific neutralizing antibody level correlation between maternal and cord blood. (E) Omicron BA1-specific neutralizing antibody level correlation between maternal and cord blood. (F) Omicron BA2-specific neutralizing antibody level correlation between maternal and cord blood. Note that for all Omicron variants, only detectable antibody levels are plotted.
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