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Publications

Journal Article Epublish

PubMed: 40768518 DOI: 10.1371/journal.ppat.1013408

Patterns and functional consequences of antibody speciation in maternal-fetal transfer of coronavirus-specific humoral immunity.

PLoS Pathog 21(8):e1013408

Authors: Andrew P Hederman, Hannah M Brookes, Harini Natarajan, Leo Heyndrickx, Kevin K Ariƫn, Joshua A Weiner, Amihai Rottenstreich, Gila Zarbiv, Dana Wolf, Tessa Goetghebuer, Arnaud Marchant, Margaret E Ackerman

Affiliations

  • Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States of America.
  • Department of Immunology and Microbiology, Geisel School of Medicine at Dartmouth, Dartmouth College, Hanover, New Hampshire, United States of America.
  • Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
  • Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
  • Department of Obstetrics and Gynecology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • Clinical Virology Unit, Hadassah University Medical Center, Jerusalem, Israel.
  • Institute for Medical Immunology, UniversitĆ© libre de Bruxelles, Charleroi, Belgium.
  • Pediatric Department, CHU St Pierre, Brussels, Belgium.

Abstract

Maternal antibodies serve as a temporary form of inherited immunity, providing humoral protection to vulnerable neonates. Whereas IgG is actively transferred up a concentration gradient via the neonatal Fc Receptor (FcRn), maternal IgA and IgM are typically excluded from fetal circulation. Further, not all IgG molecules exhibit the same transfer efficiency, being influenced by subclass, Fab and Fc domain glycosylation, antigen-specificity, and the temporal dynamics of maternal antibody responses. Here, we investigate the phenotypes and functions of maternal and cord blood antibodies induced by SARS-CoV-2 infection and compare them to those induced by mRNA vaccination, focusing on breadth of antigen recognition and antiviral functions including neutralization and effector function. While cord blood coronavirus-specific antibody functional breadth and potency appeared to be more compromised than binding breadth and potency in both groups, vaccination induced substantially greater function and breadth in cord blood than did natural infection. These functional phenotypes were associated with speciation of the maternal serum repertoires, as some IgG subpopulations were enriched while others were relatively depleted from cord blood. Relevant to the continued protection of vulnerable infants in the context of a diversifying pathogen, key observations included the greater breadth of antibody effector functions as compared to neutralization, which was associated with greater affinity for antigen and the more efficient placental transfer of IgG subclasses with better affinity to Fc receptors. This work provides new insights into the binding and functional breadth of inherited antibody responses that are likely responsible for the protection of infants born to seropositive mothers from severe SARS-CoV-2 infection despite continued viral diversification.

MeSH

Immunity, Humoral, Coronavirus, Antibody Formation, Receptors, Fc, Blood, Vaccines, Antibodies, Host-Parasite Interactions, Phenotype, Vaccination, Immunity, Infections, Infant