STUDIES OF ESCHERICHIA COLI O ANTIGEN SPECIFIC ANTIBODIES IN HUMAN MILK, MATERNAL SERUM AND CORD BLOOD

Shigella 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.

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Repertoire of naturally acquired maternal antibodies transferred to infants for protection against shigellosis

10.1101/2021.05.21.445178 ◽

2021 ◽

Author(s):

Esther Ndungo ◽

Liana R Andronescu ◽

Andrea G Buchwald ◽

Patricia Mawindo ◽

Miriam K Laufer ◽

...

Keyword(s):

Cord Blood ◽

Placental Transfer ◽

Disease Incidence ◽

Shigella Flexneri ◽

Maternal Serum ◽

Maternal Antibodies ◽

Endemic Region ◽

Specific Antibodies ◽

Maternal Immunity ◽

Epidemiological Trend

Shigella is the second leading cause of diarrheal diseases, accounting for >200,000 infections and >50,000 deaths in children under 5 years of age 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 to an early protective immunity of maternal origin and an increase in disease incidence when maternal immunity wanes. The magnitude, type, antigenic diversity and anti-microbial 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 virulent 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 IgG (very high levels) and Shigella LPS were detected in maternal and cord blood sera; efficiency of placental transfer was 100% and 60%, respectively and was associated with 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 a 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 maternal immunity wanes.

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Evidence of Human Milk Oligosaccharides in Cord Blood and Maternal-to-Fetal Transport across the Placenta

Nutrients ◽

10.3390/nu11112640 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2640 ◽

Cited By ~ 4

Author(s):

Birgit Hirschmugl ◽

Waltraud Brandl ◽

Bence Csapo ◽

Mireille van Poppel ◽

Harald Köfeler ◽

...

Keyword(s):

Human Milk ◽

Cord Blood ◽

Direct Evidence ◽

Ex Vivo ◽

Maternal Serum ◽

Human Milk Oligosaccharides ◽

Serum Samples ◽

Milk Oligosaccharides ◽

Placental Perfusion ◽

Future Studies

Human milk oligosaccharides (HMOs) are present in maternal serum in early gestation, raising the question of whether HMOs can cross the placental barrier and reach fetal circulation. Here, we aimed to detect HMOs in cord blood, and assess HMO composition and concentration in relation to maternal HMOs. In an ex-vivo placental perfusion model, we asked whether HMOs can pass over the placenta. Using HPLC, we measured HMOs in maternal serum and matching venous cord blood samples collected at delivery from normal pregnancies (n = 22). To investigate maternal-to-fetal transport, we perfused isolated placental cotyledons from term pregnancies (n = 3) with 2’-fucosyllactose (2′FL) in a double closed setting. We found up to 18 oligosaccharides typically present in maternal serum in all cord serum samples investigated. Median total cord blood HMO concentration did not differ from the concentration in maternal serum. HMO composition resembled the composition in maternal serum, with the strongest correlations for 2′FL and LDFT. After 180 min perfusion, we found 22% of maternally offered 2′FL in the fetal circuit without reaching equilibrium. Our results provide direct evidence of HMOs in cord blood, and suggest that the placenta transfers HMOs from the maternal to fetal circuit. Future studies will investigate potential differences in the transfer of specific HMOs, or in pregnancy disorders.

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The Development of IgA-Specific Antibodies to Escherichia coli O Antigen in Children

Scandinavian Journal of Immunology ◽

10.1111/j.1365-3083.1987.tb02299.x ◽

1987 ◽

Vol 26 (6) ◽

pp. 639-643 ◽

Cited By ~ 20

Author(s):

M. GLEESON ◽

A. W. CRIPPS ◽

R. L. CLANCY ◽

J. H. WLODARCZYK ◽

A. J. DOBSON ◽

...

Keyword(s):

Escherichia Coli ◽

Specific Antibodies ◽

O Antigen

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Levels of certain metals, organochlorine pesticides and dioxins in cord blood, maternal blood, human milk and some commonly used nutrients in the surroundings of the Aral Sea (Karakalpakstan, Republic of Uzbekistan)

Acta Paediatrica ◽

10.1080/08035250120060 ◽

2001 ◽

Vol 90 (7) ◽

pp. 801-808

Author(s):

O A Ataniyazova, R A Baumann, A K D L

Keyword(s):

Human Milk ◽

Cord Blood ◽

Organochlorine Pesticides ◽

Maternal Blood ◽

Aral Sea

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Maternal Vitamin D and Newborn Telomere Length

Nutrients ◽

10.3390/nu13062012 ◽

2021 ◽

Vol 13 (6) ◽

pp. 2012

Author(s):

Lisa Daneels ◽

Dries S. Martens ◽

Soumia Arredouani ◽

Jaak Billen ◽

Gudrun Koppen ◽

...

Keyword(s):

Vitamin D ◽

Cord Blood ◽

Telomere Length ◽

First Trimester ◽

Maternal Serum ◽

Adverse Outcomes ◽

Dietary Vitamin ◽

Maternal Vitamin ◽

Vitamin D Intake ◽

Diet Supplements

Nutrition is important during pregnancy for offspring health. Gestational vitamin D intake may prevent several adverse outcomes and might have an influence on offspring telomere length (TL). In this study, we want to assess the association between maternal vitamin D intake during pregnancy and newborn TL, as reflected by cord blood TL. We studied mother–child pairs enrolled in the Maternal Nutrition and Offspring’s Epigenome (MANOE) cohort, Leuven, Belgium. To calculate the dietary vitamin D intake, 108 women were asked to keep track of their diet using the seven-day estimated diet record (EDR) method. TL was assessed in 108 cord blood using a quantitative real-time PCR method. In each trimester of pregnancy, maternal serum 25-hydroxyvitamin D (25-OHD) concentration was measured. We observed a positive association (β = 0.009, p-value = 0.036) between newborn average relative TL and maternal vitamin D intake (diet + supplement) during the first trimester. In contrast, we found no association between average relative TL of the newborn and mean maternal serum 25-OHD concentrations during pregnancy. To conclude, vitamin D intake (diet + supplements), specifically during the first trimester of pregnancy, is an important factor associated with TL at birth.

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