Evidence map›Paper›PMID 40639177›Full record

ArticleVaccine2025

SARS-CoV-2 breakthrough infection during pregnancy preferentially elicits IgG4 response and enhanced placental-transfer.

Sheridan B Wagner, Monica Rincon, Katelyn E Keen, Gregory S Hawk, Nicole E Marshall, Ilhem Messaoudi

Abstract read
In one paragraph

Article in Vaccine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Sheridan B WagnerDepartment of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, United States. Electronic address: sheridan.wagner@uky.edu.
Monica RinconDepartment of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, United States. Electronic address: rincon@ohsu.edu.
Katelyn E KeenDepartment of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, United States. Electronic address: katie.keen@uky.edu.
Gregory S HawkDr. Bing Zhang Department of Statistics, University of Kentucky, Lexington, KY, United States. Electronic address: greg.hawk@uky.edu.
Nicole E MarshallDepartment of Obstetrics and Gynecology, Oregon Health & Science University, Portland, OR, United States. Electronic address: marshani@ohsu.edu.
Ilhem MessaoudiDepartment of Microbiology, Immunology, and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, United States. Electronic address: ilhem.messaoudi@uky.edu.

Funding

Dysregulation of maternal immunity during pregnancy by pregravid obesityR01AI145910 · NIAID · UNIVERSITY OF KENTUCKY · PI MESSAOUDI, ILHEM · 2019 to 2024
$3.4M
Maternal obesity and neonatal innate immunityR01AI142841 · NIAID · UNIVERSITY OF KENTUCKY · PI MESSAOUDI, ILHEM, VARLAMOV, OLEG · 2018 to 2024
$2.7M
NIAID NIH HHS R01 AI142841NIAID NIH HHS R01 AI145910
6 · The paper itself

Abstract

backgroundEmerging SARS-CoV-2 variants and waning humoral immunity have led to increased occurrences of breakthrough infection. Pregnant individuals and neonates are particularly vulnerable to adverse outcomes associated with COVID-19.

objectiveWe aimed to evaluate the maternal anti-SARS-CoV-2 IgG response and the placental transfer of antibodies to the fetus following breakthrough infection, infection in unvaccinated participants, and vaccination in the absence of infection during pregnancy.

methodsPregnant patients (n = 165) were enrolled at Oregon Health & Science University and assigned to three cohorts based on infection and vaccination status. Receptor-binding domain (RBD) and nucleocapsid protein (NP) specific IgG endpoint titers (EPT) and optical density (OD) values were determined via ELISA longitudinally in maternal blood and breastmilk, and at delivery in paired maternal, umbilical cord, and newborn blood.

resultsBreakthrough infection in vaccinated participants induced a higher maternal RBD-specific IgG response compared to infection or vaccination alone in maternal plasma and breastmilk. As reported with repeated vaccination, breakthrough infection skewed RBD-specific IgG responses toward an IgG4 response. IgG1 and IgG3 were the dominant NP-specific subclasses for both breakthrough infection and unvaccinated/infection groups. The breakthrough infection cohort had the highest newborn-to-maternal ratio of RBD-specific IgG with a strong correlation between maternal and newborn delivery titers.

conclusionBreakthrough infection during pregnancy prolongs pre-existing humoral immunity and facilitates the transplacental transfer of antibodies to the neonate, reflecting an antibody priming effect induced by prior vaccination rather than infection alone. These results warrant continued administration of updated SARS-CoV-2 vaccination during pregnancy to reduce disease severity and provide greater protection to newborns.

Indexed as

Antibodies, ViralCOVID-19Immunoglobulin GPregnancy Complications, InfectiousSARS-CoV-2AdultBreakthrough InfectionsCOVID-19 VaccinesFemaleHumansImmunity, HumoralImmunity, Maternally-AcquiredInfant, NewbornMilk, HumanPlacentaPregnancyAntibodies, ViralCOVID-19 VaccinesImmunoglobulin GSpike Glycoprotein, CoronavirusAntepartumAntibodyCOVID-19ImmunoglobulinNeonatal

Identifiers

PMID40639177
PMCPMC12377834

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.