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dc.contributor.authorNdungo, Esther
dc.contributor.authorAndronescu, Liana R
dc.contributor.authorBuchwald, Andrea G
dc.contributor.authorLemme-Dumit, Jose M
dc.contributor.authorMawindo, Patricia
dc.contributor.authorKapoor, Neeraj
dc.contributor.authorFairman, Jeff
dc.contributor.authorLaufer, Miriam K
dc.contributor.authorPasetti, Marcela F
dc.date.accessioned2021-11-03T18:46:08Z
dc.date.available2021-11-03T18:46:08Z
dc.date.issued2021-10-15
dc.identifier.urihttp://hdl.handle.net/10713/17056
dc.description.abstractShigella is the second leading cause of diarrheal diseases, accounting for >200,000 infections and >50,000 deaths in children under 5 years of age annually worldwide. The incidence of Shigella-induced diarrhea is relatively low during the first year of life and increases substantially, reaching its peak between 11 to 24 months of age. This epidemiological trend hints at an early protective immunity of maternal origin and an increase in disease incidence when maternally acquired immunity wanes. The magnitude, type, antigenic diversity, and antimicrobial activity of maternal antibodies transferred via placenta that can prevent shigellosis during early infancy are not known. To address this knowledge gap, Shigella-specific antibodies directed against the lipopolysaccharide (LPS) and virulence factors (IpaB, IpaC, IpaD, IpaH, and VirG), and antibody-mediated serum bactericidal (SBA) and opsonophagocytic killing antibody (OPKA) activity were measured in maternal and cord blood sera from a longitudinal cohort of mother-infant pairs living in rural Malawi. Protein-specific (very high levels) and Shigella LPS IgG were detected in maternal and cord blood sera; efficiency of placental transfer was 100% and 60%, respectively, and had preferential IgG subclass distribution (protein-specific IgG1 > LPS-specific IgG2). In contrast, SBA and OPKA activity in cord blood was substantially lower as compared to maternal serum and varied among Shigella serotypes. LPS was identified as the primary target of SBA and OPKA activity. Maternal sera had remarkably elevated Shigella flexneri 2a LPS IgM, indicative of recent exposure. Our study revealed a broad repertoire of maternally acquired antibodies in infants living in a Shigella-endemic region and highlights the abundance of protein-specific antibodies and their likely contribution to disease prevention during the first months of life. These results contribute new knowledge on maternal infant immunity and target antigens that can inform the development of vaccines or therapeutics that can extend protection after maternally transferred immunity wanes.en_US
dc.description.urihttps://doi.org/10.3389/fimmu.2021.725129en_US
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Immunologyen_US
dc.rightsCopyright © 2021 Ndungo, Andronescu, Buchwald, Lemme-Dumit, Mawindo, Kapoor, Fairman, Laufer and Pasetti.en_US
dc.subjectShigella antibodiesen_US
dc.subjectinfant immunityen_US
dc.subjectmaternal antibodiesen_US
dc.subjectnaturally acquired immunityen_US
dc.subjecttransplacental antibody transferen_US
dc.titleRepertoire of Naturally Acquired Maternal Antibodies Transferred to Infants for Protection Against Shigellosisen_US
dc.typeArticleen_US
dc.identifier.doi10.3389/fimmu.2021.725129
dc.identifier.pmid34721387
dc.source.volume12
dc.source.beginpage725129
dc.source.endpage
dc.source.countrySwitzerland


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