Cord blood antibodies following maternal coronavirus disease 2019 vaccination during pregnancy

Mithal, Leena B.; Otero, Sebastián; Shanes, Elisheva D; Goldstein, Jeffery A.; Miller, Emily S.

doi:10.1016/j.ajog.2021.03.035

Cited by 137 publications

(221 citation statements)

References 5 publications

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“…12 Antibody transfer was also reported. 12,14,15,17,18,20,21 Cord blood antibody and maternal antibody levels were about equal. 18 Additionally, latency and number of doses were correlated with the antibody transfer strength.…”

Section: Main Findingmentioning

confidence: 94%

“…All pregnant women reported receiving mRNA vaccine, either Pfizer-BioNTech or Moderna vaccine, except for four pregnant women who received unknown types of vaccine. 18 Some studies compared vaccinated pregnant women with unvaccinated pregnant women, either naturally infected or not infected, or vaccinated non-pregnant women. The efficacy outcome was desribed as infection rate, while immunogenicity was described as maternal antibody response, fetal antibody response, and transplacental antibody transfer.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…14 Having received the second vaccine dose was positively correlated with infant IgG level (β=19.0 (95%CI 7.1-30.8)). 18 In addition to doses, the interval from vaccination to delivery was correlated with IgG transfer ratio and infant IgG level. Increased latency from vaccination to delivery was positively correlated with IgG transfer ratio (β=0.2 (95%CI 0.1-0.2)) and infant IgG level (β=2.9 (95%CI 0.7-5.1)).…”

Section: Antibody Transfermentioning

confidence: 99%

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Covid-19 Vaccination in Pregnancy: A Systematic Review

Pratama

Wafa

Budi

et al. 2021

Preprint

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Objective: Pregnancy is a risk factor for severe Covid-19. Looking for safe vaccines that evoke protective maternal and fetal antibody response is important. Methods: We searched from registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the EU Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, and Springer) up until June 20, 2021. Articles were selected based on inclusion and exclusion criteria after duplicates were removed. Infection rate, maternal antibody response, placental antibody transfer, and adverse events were described. This systematic review was performed with quality assessment and semi-quantitative synthesis according to PRISMA guidelines. Results: Twelve observational studies with a total of 40.509 pregnant women included. The mRNA based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infections (p=0.0004). Both vaccines did not affect pregnancy, delivery, and neonatal outcomes. The most commonly encountered adverse reactions are injection-site pain, fatigue, and headache but only transient. Antibody responses were rapid after the prime dose of vaccines. After booster, antibody responses were higher and associated with better placental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and better antibody transfer ratio. Conclusions: The Pfizer-BioNTech and Moderna vaccines are efficacious for preventing future SARS-CoV-2 infections. These vaccines can be considered as a safe option for pregnancy and their fetus. Two doses of vaccines were recommended for more robust maternal and fetal antibody responses. Longer latency was associated with higher fetal antibody responses.

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Section: Main Findingmentioning

confidence: 94%

Section: Study Characteristicsmentioning

confidence: 99%

Section: Antibody Transfermentioning

confidence: 99%

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Covid-19 Vaccination in Pregnancy: A Systematic Review

Pratama

Wafa

Budi

et al. 2021

Preprint

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“…Linked to highly effective protection against severe COVID-19 disease in non-pregnant populations (14,15), both mRNA platforms clearly lead to the induction of robust immunity in men and non-pregnant women across age groups Walsh et al, 2020). Moreover, emerging data suggest that mRNA vaccines also induce comparable antibody titers and neutralization in pregnant and lactating women, linked to transfer of antibodies to neonates (16,17). The explosion of multiple vaccine platforms, coupled with the availability of novel high-dimensional antibody profiling technologies, enables the unprecedented opportunity to dissect the de novo mRNA vaccineinduced immune response in this vulnerable population.…”

Section: Introductionmentioning

confidence: 99%

COVID-19 mRNA vaccines drive differential Fc-functional profiles in pregnant, lactating, and non-pregnant women

Atyeo

DeRiso

Davis

et al. 2021

Preprint

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Significant immunological changes occur throughout pregnancy to tolerize the mother and allow growth of the fetal graft. However, additional local and systemic immunological adaptations also occur, allowing the maternal immune system to continue to protect the dyad against foreign invaders both during pregnancy and after birth through lactation. This fine balance of tolerance and immunity, along with physiological and hormonal changes, contribute to increased susceptibility to particular infections in pregnancy, including more severe COVID-19 disease. Whether these changes also make pregnant women less responsive to vaccination or induce altered immune responses to vaccination remains incompletely understood. To holistically define potential changes in vaccine response during pregnancy and lactation, we deeply profiled the humoral vaccine response in a group of pregnant and lactating women and non-pregnant age-matched controls. Vaccine-specific titers were comparable, albeit slightly lower, between pregnant and lactating women, compared to non-pregnant controls. Among pregnant women, we found higher antibody titers and functions in those vaccinated with the Moderna vaccine. FcR-binding and antibody effector functions were induced with delayed kinetics in both pregnant and lactating women compared to non-pregnant women. Antibody boosting resulted in high FcR-binding titers in breastmilk. These data point to an immune resistance to generate highly inflammatory antibodies during pregnancy and lactation, and a critical need to follow prime/boost timelines in this vulnerable population to ensure full immunity is attained.

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“…Pregnant women were excluded from initial clinical trials for COVID-19 vaccines [1][2] , thus the immunologic response to vaccination in pregnancy and the transplacental transfer of maternal antibodies are just beginning to be studied [4][5] .…”

Section: Discussionmentioning

confidence: 99%

Antibody response to SARS-CoV-2 mRNA vaccines in pregnant women and their neonates

Prabhu

Murphy

Sukhu

et al. 2021

Preprint

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Pregnant women were excluded from initial clinical trials for COVID-19 vaccines1-2, thus the immunologic response to vaccination in pregnancy and the transplacental transfer of maternal antibodies are just beginning to be studied4-5. Methods: Between January 28 and March 31, 2021, we studied 122 pregnant women and their neonates at time of birth. All women had received one or both doses of a messenger RNA (mRNA)-based COVID-19 vaccine. Fifty-five women received only one dose of the vaccine and 67 women received both doses of the vaccine by time of giving birth. Eighty-five women received the Pfizer-BioNTech vaccine, while 37 women received the Moderna vaccine. All women tested negative for SARS-CoV-2 infection using reverse-transcriptase PCR on nasopharyngeal swabs, and none reported any COVID-19 symptoms at the time of admission for birth. Semi-quantitative testing for antibodies against S-Receptor Binding Domain (RBD) (ET HealthCare)3 was performed on sera of maternal peripheral blood and neonatal cord blood at the time of delivery to identify antibodies mounted against the vaccine. All women tested negative for antibodies against the Nucleocapsid Protein (NP) antigen (Roche Diagnostics EUA) to ensure that the antibodies detected were not produced in response to past SARS-CoV-2 infection. Relationship between IgG antibody levels over time was studied using ANOVA with Tukey posthoc. Relationship between maternal and neonatal IgG levels was studied using Pearson correlation analysis and linear regression on log2-scaled serological values. Relationship between IgG placental transfer ratio (neonatal/maternal) vs. time was studied using Pearson correlation analysis and linear regression on log2-scaled serological values and days. Serology levels represented as log2+1. Statistical analysis was performed using R 3.6.3, RStudio 1.1.463. The study was approved by the Weill Cornell Medicine institutional review board. Results: Pregnant women vaccinated with mRNA-based COVID-19 vaccines during pregnancy and tested at time of birth had detectable immunoglobulin (Ig)G and IgM response. Eighty-seven women tested at birth produced only an IgG response, and 19 women produced both an IgM and IgG response. Sixteen women tested at birth had no detectable antibody response, and they were all within four weeks after vaccination dose 1 (Figure 1A). There was an increase over time in the number of women that mounted an antibody response, as well as the number of women that demonstrated passive immunity to their neonates (Figure 1A). All women and their neonates, except for one neonate, had detectable IgG antibodies by 4 weeks after maternal first dose of vaccination (Figure 1A). 43.6% (24/55) of neonates born to women that received only one vaccine dose had detectable IgG, while 98.5% (65/67) of neonates born to women that received both vaccine doses had detectable IgG. The IgG levels in pregnant women increased weekly from two weeks after first vaccine dose (p=0.0047;0.019), as well as between the first and second weeks after the second vaccine dose (p=2e-07) (Figure 1B). Maternal IgG levels were linearly associated with neonatal IgG levels (R=0.89, p<2.2e-16) (Figure 2A). Placental transfer ratio correlated with the weeks that elapsed since maternal second dose of vaccine (R=0.8, p=2.6e-15) (Figure 2B). Discussion: mRNA-based COVID-19 vaccines in pregnant women lead to maternal antibody production as early as 5 days after the first vaccination dose, and passive immunity to the neonate as early as 16 days after the first vaccination dose. The increasing levels of maternal IgG over time, and the increasing placental IgG transfer ratio over time suggest that timing between vaccination and birth may be an important factor to consider in the vaccination strategies of pregnant women. Further studies are needed to understand the factors that influence transplacental transfer of IgG antibody, as well as the protective nature of these antibodies.

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Cord blood antibodies following maternal coronavirus disease 2019 vaccination during pregnancy

Cited by 137 publications

References 5 publications

Covid-19 Vaccination in Pregnancy: A Systematic Review

Covid-19 Vaccination in Pregnancy: A Systematic Review

COVID-19 mRNA vaccines drive differential Fc-functional profiles in pregnant, lactating, and non-pregnant women

Antibody response to SARS-CoV-2 mRNA vaccines in pregnant women and their neonates

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