Neutralizing and binding antibody responses to SARS-CoV-2 with hybrid immunity in pregnancy.

Hybrid immunity against SARS-CoV-2 has not been well studied in pregnancy. We conducted a comprehensive analysis of neutralizing antibodies (nAb) and binding antibodies in pregnant individuals who received mRNA vaccination, natural infection, or both. A third vaccine dose augmented nAb levels compared to the two-dose regimen or natural infection alone; this effect was more pronounced in hybrid immunity.

Milk antibody response after 3 COVID-19 vaccine and SARS-CoV-2 infection and implications for infant protection.

Little is known about the persistence of human milk anti-SARS-CoV-2 antibodies after 2 and 3 vaccine doses and infection following 3 dose. In this study, human milk, saliva, and blood samples were collected from 33 lactating individuals before and after vaccination and infection. Antibody levels were measured using ELISA and symptoms were assessed using questionnaires.

Assessment of Adverse Reactions, Antibody Patterns, and 12-month Outcomes in the Mother-Infant Dyad After COVID-19 mRNA Vaccination in Pregnancy.

Importance: Longitudinal data on COVID-19 messenger RNA (mRNA) vaccine reactogenicity and immunogenicity in pregnancy and for the mother-infant dyad are needed.

Objective: To examine COVID-19 mRNA vaccine reactogenicity and immunogenicity in pregnancy and observe longitudinal maternal and infant outcomes.

Design, Setting, And Participants: This prospective cohort study of pregnant individuals enrolled in the COVID-19 Vaccination in Pregnancy and Lactation study from December 1, 2020, through December 31, 2021, with follow-up through March 31, 2022, was conducted at a large academic medical center in an urban metropolitan area in California.

Nirmatrelvir-Ritonavir (Paxlovid) for Mild Coronavirus Disease 2019 (COVID-19) in Pregnancy and Lactation.

Nirmatrelvir-ritonavir (Paxlovid) is recommended to reduce the risk of hospitalization from coronavirus disease 2019 (COVID-19) in pregnancy. Data on use in pregnancy, including prescribing patterns and patient experience (adverse effects, incidence of rebound), are limited. We performed a cross-sectional study in which we surveyed a cohort of vaccinated pregnant or lactating individuals with breakthrough COVID-19.

Milk antibody response after 3rd dose of COVID-19 mRNA vaccine and SARS-CoV-2 breakthrough infection and implications for infant protection.

Anti-SARS-CoV-2 antibodies have been found in human-milk after COVID-19 infection and vaccination. However, little is known about their persistence in milk after booster vaccination and breakthrough infection. In this study, human-milk, saliva and blood samples were collected from 33 lactating individuals before and after mRNA-based vaccination and COVID-19 breakthrough infections.

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and infancy.

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. Here, we evaluate the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during late pregnancy. We find no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery.

Effects of Vaccination Against Influenza, Pertussis, and COVID-19 on Human Milk Antibodies: Current Evidence and Implications for Health Equity.

Human milk contains three antibody classes that confer mucosal immunity to the breastfed infant: secretory IgA (SIgA), secretory IgM (SIgM), and IgG. Influenza and pertussis vaccines administered during pregnancy induce pathogen specific SIgA and IgG responses in human milk that have been shown to protect the breastfed infant from these respiratory illnesses. In addition, mRNA vaccines against the SARS-CoV-2 virus administered during pregnancy and lactation induce anti-SARS-CoV-2 IgG and IgA responses in human milk.

Neutralizing antibody activity against SARS-CoV-2 variants in gestational age-matched mother-infant dyads after infection or vaccination.

Pregnancy confers unique immune responses to infection and vaccination across gestation. To date, there are limited data comparing vaccine- and infection-induced neutralizing Abs (nAbs) against COVID-19 variants in mothers during pregnancy. We analyzed paired maternal and cord plasma samples from 60 pregnant individuals.

Cellular and transcriptional diversity over the course of human lactation.

Human breast milk (hBM) is a dynamic fluid that contains millions of cells, but their identities and phenotypic properties are poorly understood. We generated and analyzed single-cell RNA-sequencing (scRNA-seq) data to characterize the transcriptomes of cells from hBM across lactational time from 3 to 632 d postpartum in 15 donors. We found that the majority of cells in hBM are lactocytes, a specialized epithelial subset, and that cell-type frequencies shift over the course of lactation, yielding greater epithelial diversity at later points.

Early non-neutralizing, afucosylated antibody responses are associated with COVID-19 severity.

A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated immunoglobulin G (IgG) antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. To study the biology of afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc-gamma receptor (FcγR) interactions could regulate inflammation in the lung.

Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses.

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that have mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and early infancy.

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. We evaluated the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during pregnancy. We found no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery.

Evaluation of transplacental transfer of mRNA vaccine products and functional antibodies during pregnancy and early infancy.

Studies are needed to evaluate the safety and effectiveness of mRNA SARS-CoV-2 vaccination during pregnancy, and the levels of protection provided to their newborns through placental transfer of antibodies. We evaluated the transplacental transfer of mRNA vaccine products and functional anti-SARS-CoV-2 antibodies during pregnancy and early infancy in a cohort of 20 individuals vaccinated during pregnancy. We found no evidence of mRNA vaccine products in maternal blood, placenta tissue, or cord blood at delivery.

COVID-19 mRNA Vaccination in Lactation: Assessment of Adverse Events and Vaccine Related Antibodies in Mother-Infant Dyads.

Background: Data regarding symptoms in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines.

Methods: From a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires.

COVID-19 mRNA Vaccination in Lactation: Assessment of adverse events and vaccine related antibodies in mother-infant dyads.

Background: Data regarding adverse events observed in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines.

Methods: From a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires.

Evaluation of Messenger RNA From COVID-19 BTN162b2 and mRNA-1273 Vaccines in Human Milk.

This cohort study analyzes milk samples from lactating mothers to determine if COVID-19 vaccine–related messenger RNA was detectable in human milk after vaccination.

Structurally and functionally distinct early antibody responses predict COVID-19 disease trajectory and mRNA vaccine response.

Unlabelled: A damaging inflammatory response is strongly implicated in the pathogenesis of severe COVID-19 but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated, anti-SARS-CoV-2 IgG predicted progression from mild, to more severe COVID-19. In contrast to the antibody structures that predicted disease progression, antibodies that were elicited by mRNA SARS-CoV-2 vaccines were low in Fc afucosylation and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG.

Genetic and Physiological Factors Affecting Human Milk Production and Composition.

Human milk is considered the optimal nutrition for infants as it provides additional attributes other than nutritional support for the infant and contributes to the mother's health as well. Although breastfeeding is the most natural modality to feed infants, nowadays, many mothers complain about breastfeeding difficulties. In addition to environmental factors that may influence lactation outcomes including maternal nutrition status, partner's support, stress, and latching ability of the infant, intrinsic factors such as maternal genetics may also affect the quantitative production and qualitative content of human milk.

Alterations in ZnT1 expression and function lead to impaired intracellular zinc homeostasis in cancer.

Zinc is vital for the structure and function of ~3000 human proteins and hence plays key physiological roles. Consequently, impaired zinc homeostasis is associated with various human diseases including cancer. Intracellular zinc levels are tightly regulated by two families of zinc transporters: ZIPs and ZnTs; ZIPs import zinc into the cytosol from the extracellular milieu, or from the lumen of organelles into the cytoplasm.

Correction: Demonstrating aspects of multiscale modeling by studying the permeation pathway of the human ZnT2 zinc transporter.

[This corrects the article DOI: 10.1371/journal.pcbi.

ZnT2 is an electroneutral proton-coupled vesicular antiporter displaying an apparent stoichiometry of two protons per zinc ion.

Zinc is a vital trace element crucial for the proper function of some 3,000 cellular proteins. Specifically, zinc is essential for key physiological processes including nucleic acid metabolism, regulation of gene expression, signal transduction, cell division, immune- and nervous system functions, wound healing, and apoptosis. Consequently, impairment of zinc homeostasis disrupts key cellular functions resulting in various human pathologies.

High proportion of transient neonatal zinc deficiency causing alleles in the general population.

Loss of function (LoF) mutations in the zinc transporter SLC30A2/ZnT2 result in impaired zinc secretion into breast milk consequently causing transient neonatal zinc deficiency (TNZD) in exclusively breastfed infants. However, the frequency of TNZD causing alleles in the general population is yet unknown. Herein, we investigated 115 missense SLC30A2/ZnT2 mutations from the ExAC database, equally distributed in the entire coding region, harboured in 668 alleles in 60 706 healthy individuals of diverse ethnicity.

Demonstrating aspects of multiscale modeling by studying the permeation pathway of the human ZnT2 zinc transporter.

Multiscale modeling provides a very powerful means of studying complex biological systems. An important component of this strategy involves coarse-grained (CG) simplifications of regions of the system, which allow effective exploration of complex systems. Here we studied aspects of CG modeling of the human zinc transporter ZnT2.

The role of the zinc transporter SLC30A2/ZnT2 in transient neonatal zinc deficiency.

Breast milk is the optimal nutrient mix for infants until the age of 6 months. However, in some cases, due to genetic alterations as well as nutrient deficiencies in nursing mothers, infants may suffer from inadequate levels of micronutrients upon exclusive breastfeeding. In this respect, transient neonatal zinc deficiency (TNZD) is caused by loss-of-function mutations in the zinc transporter SLC30A2/ZnT2 gene, resulting in poor secretion of zinc into the breast milk.