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

2021 ◽  
Author(s):  
Esther Ndungo ◽  
Liana R Andronescu ◽  
Andrea G Buchwald ◽  
Patricia Mawindo ◽  
Miriam K Laufer ◽  
...  

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.

2021 ◽  
Vol 12 ◽  
Author(s):  
Esther Ndungo ◽  
Liana R. Andronescu ◽  
Andrea G. Buchwald ◽  
Jose M. Lemme-Dumit ◽  
Patricia Mawindo ◽  
...  

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.


1976 ◽  
Vol 65 (2) ◽  
pp. 216-224 ◽  
Author(s):  
B. CARLSSON ◽  
L. GOTHEFORS ◽  
S. AHLSTEDT ◽  
L. A. HANSON ◽  
J. WINBERG

2019 ◽  
Vol 25 (5) ◽  
pp. 496-504 ◽  
Author(s):  
Naïm Bouazza ◽  
Frantz Foissac ◽  
Déborah Hirt ◽  
Saïk Urien ◽  
Sihem Benaboud ◽  
...  

Background: Drug prescriptions are usual during pregnancy, however, women and their fetuses still remain an orphan population with regard to drugs efficacy and safety. Most xenobiotics diffuse through the placenta and some of them can alter fetus development resulting in structural abnormalities, growth or functional deficiencies. Methods: To summarize the different methodologies developed towards the prediction of fetal drug exposure. Results: Neonatal cord blood concentration is the most specific measurement of the transplacental drug transfer at the end of pregnancy. Using the cord blood and mother drug concentrations altogether, drug exchanges between the mother and fetus can be modeled and quantified via a population pharmacokinetic analysis. Thereafter, it is possible to estimate the fetus exposure and the fetus-to-mother exposure ratio. However, the prediction of placental transfer before any administration to pregnant women is desirable. Animal studies remain difficult to interpret due to structural and functional inter-species placenta differences. The ex-vivo perfusion of the human placental cotyledon is the method of reference to study the human placental transfer of drugs because it is thought to mimic the functional placental tissue. However, extrapolation of data to in vivo situation remains difficult. Some research groups have extensively worked on physiologically based models (PBPK) to predict fetal drug exposure and showed very encouraging results. Conclusion: PBPK models appeared to be a very promising tool in order to predict fetal drug exposure in-silico. However, these models mainly picture the end of pregnancy and knowledge regarding both, development of the placental permeability and transporters is strongly needed.


Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2012
Author(s):  
Lisa Daneels ◽  
Dries S. Martens ◽  
Soumia Arredouani ◽  
Jaak Billen ◽  
Gudrun Koppen ◽  
...  

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.


2021 ◽  
Vol 224 (2) ◽  
pp. S64-S65
Author(s):  
Fatima A. Estrada Trejo ◽  
Hadley Pfalzgraf ◽  
Avish Arora ◽  
Aakash Mahant Mahant ◽  
Betsy Herold

Author(s):  
Jumpei Saito ◽  
Asako Mito ◽  
Naho Yakuwa ◽  
Kayoko Kaneko ◽  
Hiroyo Kawasaki ◽  
...  

Cytokine X ◽  
2021 ◽  
pp. 100052
Author(s):  
Anne FLOECK ◽  
Nina FERRARI ◽  
Christine JOISTEN ◽  
Maria T. PUTH ◽  
Brigitte STRIZEK ◽  
...  

2019 ◽  
Vol 80 ◽  
pp. 99-106 ◽  
Author(s):  
Aijing Li ◽  
Taifeng Zhuang ◽  
Jianbo Shi ◽  
Yong Liang ◽  
Maoyong Song

2019 ◽  
Author(s):  
Laura E. Doepker ◽  
Cassandra A. Simonich ◽  
Duncan Ralph ◽  
Theodore Gobillot ◽  
Meghan Garrett ◽  
...  

AbstractInfants of HIV positive mothers can acquire HIV infection by various routes, but even in the absence of antiviral treatment, the majority of these infants do not become infected. There is evidence that maternal antibodies may provide some protection from infection, but gestational maternal antibodies have not yet been characterized in detail. One of the most studied vertically-infected infants is BG505, as the virus from this infant yielded an Envelope protein that was successfully developed as a stable trimer. Here, we isolated and characterized 39 HIV-specific neutralizing monoclonal antibodies (nAbs) from MG505, the mother of BG505, at a time point just prior to vertical transmission. These nAbs belonged to 21 clonal families, employed a variety of VH genes, many were specific for the HIV-1 Env V3 loop, and this V3 specificity correlated with measurable antibody-dependent cellular cytotoxicity (ADCC) activity. The isolated nAbs did not recapitulate the full breadth of heterologous nor autologous virus neutralization by contemporaneous plasma. Notably, we found that the V3-targeting nAb families neutralized one particular maternal Env variant even though all tested variants had low V3 sequence diversity and were measurably bound by these nAbs. None of the nAbs neutralized the BG505 transmitted virus. Furthermore, the MG505 nAb families were found at relatively low frequencies within the maternal B cell repertoire: all less than 0.25% of total IgG sequences. Our findings demonstrate the diversity of HIV-1 nAbs that exist within a single mother, resulting in a collection of antibody specificities that can shape the transmission bottleneck.ImportanceMother-to-child-transmission of HIV-1 offers a unique setting in which maternal antibodies both within the mother and passively-transferred to the infant are present at the time of viral exposure. Untreated HIV-exposed human infants are infected at a rate of 30-40%, meaning that some infants do not get infected despite continued exposure to virus. Since the potential of HIV-specific immune responses to provide protection against HIV is a central goal of HIV vaccine design, understanding the nature of maternal antibodies may provide insights into immune mechanisms of protection. In this study, we isolated and characterized HIV-specific antibodies from the mother of an infant whose transmitted virus has been well studied.


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