Early versus late third trimester maternal SARS-CoV-2 BNT162b2 mRNA immunization maximizes transplacental antibody transfer and neonatal neutralizing antibody levels

  1. Amihai Rottenstreich
  2. Gila Zarbiv
  3. Esther Oiknine-Djian
  4. Olesya Vorontsov
  5. Roy Zigron
  6. Geffen Kleinstern
  7. Dana G. Wolf
  8. Shay Porat

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Abstract

Objective

We aimed to assess the impact of early versus late third trimester maternal SARS-CoV-2 vaccination on transplacental transfer and neonatal levels of SARS-CoV-2 antibodies.

Methods

Maternal and cord blood sera were collected following term delivery after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination, with the first vaccine dose administered during 27-36 weeks gestation. SARS-CoV-2 spike protein (S) and receptor binding domain (RBD)- specific, IgG levels and neutralizing potency were evaluated in maternal and cord blood samples.

Results

The study cohort consisted of 171 parturients (median age, 31 years; median gestational age, 39.7 weeks): 83 (48.5%) immunized at early 3 rd trimester (1 st dose at 27-31 weeks), and 88 (51.5%) immunized at late 3 rd trimester (1 st dose at 32-36 weeks). All mother-infant paired sera were positive for anti S- and anti-RBD-specific IgG. Anti-RBD-specific IgG concentrations in neonatal sera were higher following early versus late 3 rd trimester vaccination and were positively correlated with increasing time since vaccination (r=□0.26; P=0.001). The median placental transfer ratios of anti-S and anti-RBD specific IgG were increased following early versus late 3 rd trimester immunization (anti-S ratio:1.3 vs. 0.9, anti-RBD-specific ratio:2.3 vs. 0.7, P<0.001). Neutralizing antibodies placental transfer ratio was greater following early versus late 3 rd trimester immunization (1.9 vs. 0.8, P<0.001), and was positively associated with longer duration from vaccination (r=□0.77; P<0.001).

Conclusions

Early- as compared to late third trimester maternal SARS-CoV-2 immunization enhanced transplacental antibody transfer and increased neonatal neutralizing antibody levels. Our findings highlight that vaccination of pregnant women early in the third trimester may optimize neonatal seroprotection.

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  1. ScreenIT

    SciScore for 10.1101/2021.08.30.21262875: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: The institutional review board of the Hadassah Medical Center approved this study (HMO-0064-21).
    Consent: Laboratory Methods: Maternal and cord blood sera were collected following delivery after obtaining written informed consent.
    Sex as a biological variableStudy Population: A prospective study following women admitted for delivery was performed during February-April 2021 at Hadassah Medical Center, a tertiary-care university affiliated hospital in Jerusalem, Israel with over 10,000 deliveries annually.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    For a subset of mother/newborn dyads, neutralizing antibody titers against SARS-CoV-2 were defined using a wild-type SARS-CoV-2 virus microneutralization assay as previously described [21], with minor modifications.
    SARS-CoV-2
    suggested: None
    SARS-CoV-2 IgM antibodies were not detected in any of the neonates, and were detected in 30 (17.5%) parturients, all of whom were vaccinated late in the 3rd trimester.
    SARS-CoV-2 IgM
    suggested: (Bethyl Cat# E88-302, RRID:AB_2892019)
    There was a negative association between maternal anti-S and anti-RBD-specific IgG concentrations and the time lapsed since immunization (r=□-0.37; P□<0.001 and r=□-0.41; P□<0.001, respectively; Figure 2C, D) Neonatal concentrations of anti-S IgG antibodies did not differ in relation to maternal third trimester immunization timing (Figure 2E, 3C).
    anti-S
    suggested: (Imported from the IEDB Cat# 3C12-Fc, RRID:AB_2847975)
    anti-RBD-specific IgG
    suggested: None
    anti-S IgG
    suggested: None
    Placental transfer ratio of neutralizing SARS-CoV-2 antibodies was significantly higher following early 3rd trimester immunization as compared to late 3rd trimester immunization (median 1.9 vs. 0.8, P<0.001) (Figure 5C), and was positively associated with increasing time from vaccination (r=□0.77; P<0.001; Figure 5D) and anti-RBD placental transfer ratio (r=□0.82; P<0.001; Figure 5E)
    anti-RBD placental transfer ratio
    suggested: None
    Software and Algorithms
    SentencesResources
    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.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    The data were analyzed using Software Package for Statistics and Simulation (IBM SPSS version 24, IBM Corp, Armonk, NY).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Nevertheless, this study has several caveats. First, the observational single-center design of the study may limit the generalizability of our findings. Second, the effects of maternal immunization in early pregnancy as well as of the impact of other SARS-CoV-2 vaccines on transplacental antibody transfer dynamics remain to be determined. The former could provide maternal protection against COVID-19 through the longer course of pregnancy and may benefit preterm infants. Finally, vaccine-induced maternally-derived antibodies might blunt the infant humoral immune response to future vaccination; while the clinical significance of this interference effect is largely unknown [28], it should be acknowledged and further explored.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.08.30.21262875v1 on medRxiv