Milk sIgA Research Articles

Effect of Exclusive Breastfeeding on the Risk of ARI in Under-Five Children: Literature Review

Introduction: Acute Respiratory Infection (ARI) is a major health problem in under-five children which can cause death. Exclusive breastfeeding can prevent infections, one of which is ARI. Objective: This study aims to examine the relationship between exclusive breastfeeding and the risk of ARI in under-five children. Method: This research uses a literature review approach which measures the relationship between exclusive breastfeeding and the risk of ARI in under-five children. The data source uses secondary data in the form of articles obtained through two databases, namely Scopus and Springer Link. Result: There are 5 articles that meet the requirements for research. Four out of five articles prove that exclusive breastfeeding reduces the risk of children under five getting ARI. The finding of a higher risk of ARI in the group of children under five who are not exclusively breastfed can be caused by a decrease in the immunity of children under five, seeing that breast milk is proven to fight infection. The content of sIgA and lactoferrin in breast milk and immunization can increase the immune system in children under five who suffer from ARI. Conclusion: Breast milk has nutrients in it which are useful for preventing infectious diseases, such as ARI and pneumonia in children under five. Given the influence on the health of children under five, the findings of this study demonstrate the need for improvements in breastfeeding programs, with a particular emphasis on exclusive breastfeeding and ARI management. There is a need for widely accessible health workers, information, and services connected to care for moms.

In vivo antiviral efficacy of LCTG-002, a pooled, purified human milk secretory IgA product, against SARS-CoV-2 in a murine model of COVID-19.

Immunoglobulin A (IgA) is the most abundant antibody (Ab) in human mucosae, with secretory form (sIgA) being dominant and uniquely stable. sIgA is challenging to produce recombinantly but is naturally found in human milk, which could be considered a global resource for this biologic, justifying its development as a mucosal therapeutic. Presently, SARS-CoV-2 was utilized as a model mucosal pathogen, and methods were developed to efficiently extract human milk sIgA from donors who were naïve to SARS-CoV-2 or had recovered from infection that elicited high-titer anti-SARS-CoV-2 Spike sIgA in their milk (pooled to make LCTG-002). Mass spectrometry determined that proteins with a relative abundance of 1% or greater were all associated with sIgA. Western blot demonstrated that all batches consisted predominantly of sIgA. Compared to control IgA, LCTG-002 demonstrated significantly higher Spike binding (mean endpoint of 0.87 versus 5.87). LCTG-002 was capable of blocking the Spike receptor-binding domain - angiotensin-converting enzyme 2 (ACE2) interaction with significantly greater potency compared to control (mean LCTG-002 IC50 154ug/mL versus 50% inhibition not achieved for control), and exhibited significant neutralization activity against Spike-pseudotyped virus infection (mean LCTG-002 IC50 49.8ug/mL versus 114.5ug/mL for control). LCTG-002 was tested for its capacity to reduce viral lung burden in K18+hACE2 transgenic mice inoculated with SARS-CoV-2. LCTG-002 significantly reduced SARS-CoV-2 titers compared to control when administered at 0.25 mg/day or 1 mg/day, with a maximum TCID50 reduction of 4.9 logs. This innovative study demonstrates that LCTG-002 is highly pure and efficacious in vivo, supporting further development of milk-derived, polyclonal sIgA therapeutics.

Breast milk oxytocin and s-IgA modulate infant biomarkers and social engagement; The role of maternal anxiety

Breastfeeding has long been known to improve infants' health and mental development and to enhance the mother-infant bond, but much less research focused on the biological composition of breast milk and its associations with the infant's biomarkers and social development. In this exploratory study, we measured oxytocin (OT) and secretory immunoglobulin-A (s-IgA), the most abundant antibody in breast milk, and evaluated their associations with the same biomarkers in infant saliva and, consequently, with infant social engagement behavior. Fifty-five mother-infant dyads were home-visit and OT and s-IgA were assessed from breast milk and from infant saliva before and after a free-play interaction. Infant social behavior was coded offline using the Coding Interactive Behavior (CIB) and maternal anxiety self-reported. A path model revealed that mother's breast milk s-IgA impacted child social engagement via its links with child OT. In parallel, maternal breast milk OT was linked with infant social behavior through its association with the infant's immunity. This path was moderated by maternal anxiety; only in cases of high anxiety breast milk OT was positively connected to infant s-IgA. Our study, the first to measure OT and s-IgA in both breast milk and infant saliva in relation to observed social behavior, underscores the need for much further research on the dynamic interplay between breast milk composition, infant biomarkers, maternal mental health, and infant social outcomes. Results may suggest that biological systems in breast milk integrate to prepare infants to function in their social ecology through bio-behavioral feedback loops that signal the degree of stress in the environment.

The Persistence of Specific Immunoglobulin A Against SARS-CoV-2 in Human Milk After Maternal COVID-19 Vaccination.

Objectives: To investigate SARS-CoV-2 specific immunoglobulin A (sIgA) in breast milk of Thai mothers post COVID-19 vaccination and/or SARS-CoV-2 infection, and to compare the sIgA among lactating mothers with varying COVID-19 vaccination regimes. Materials and Methods: A longitudinal study was conducted in lactating mothers receiving ≥2 doses of COVID-19 vaccine or confirming SARS-CoV-2-positive test as a part of an infant feeding survey. Vaccination and infection details were collected through questionnaires and interviews. Self-collected breast milk samples (30 mL) at 1, 3, and 6 months postvaccination or infection were analyzed for sIgA through enzyme-linked immunosorbent assay (ELISA). Results: Eighty-eight lactating mothers (152 milk samples), average age of 30.7 ± 6.2 years, were recruited. Fifty-five percent of milk samples were from lactating mothers with both SARS-CoV-2 infection and vaccination (hybrid immunity); 40% were from those with vaccination alone (COVID naïve). Sixty percent of lactating mothers received mixed types of vaccines. Median sIgA ratio in breast milk was 2.67 (0.82-7.85). Breast milk sIgA at 1, 3, and 6 months were higher in mothers with hybrid immunity than in COVID naïve (geometric mean [95% confidence interval]: 3.30 [2.06-5.29] versus 1.04 [0.52-2.04], 3.39 [2.24-5.13] versus 1.26 [0.77-2.06], 4.29 [3.04-6.06] versus 1.33 [0.74-2.42], respectively). No significant differences were observed among various vaccination regimes. Conclusion: sIgA against SARS-CoV-2 was detected in breast milk for up to 6 months after immunization together with infection at a greater level than after immunization or infection alone. This immunity could be transferred and protective against SARS-CoV-2 infection. Discontinuation of breastfeeding among mothers who received COVID vaccination or experienced infection should be discouraged. Clinical Trial Registration number: TCTR20220215012.

A novel recombinant S-based subunit vaccine induces protective immunity against porcine deltacoronavirus challenge in piglets.

As an emerging porcine enteropathogenic coronavirus that has the potential to infect humans, porcine deltacoronavirus (PDCoV) is receiving increasing attention. However, no effective commercially available vaccines against this virus are available. In this work, we designed a spike (S) protein and receptor-binding domain (RBD) trimer as a candidate PDCoV subunit vaccine. We demonstrated that S protein induced more robust humoral and cellular immune responses than the RBD trimer in mice. Furthermore, the protective efficacy of the S protein was compared with that of inactivated PDCoV vaccines in piglets and sows. Of note, the immunized piglets and suckling pig showed a high level of NAbs and were associated with reduced virus shedding and mild diarrhea, and the high level of NAbs was maintained for at least 4 months. Importantly, we demonstrated that S protein-based subunit vaccines conferred significant protection against PDCoV infection.

THE CONTENT OF SECRETORY IMMUNOGLOBULIN A IN BREAST MILK OF PATIENTS WITH LACTATIONAL MASTITIS

Introduction. The protective function of breast milk is provided by a number of specific and non-specific anti-infective factors: secretory immunoglobulin A, immunoglobulins A, G, M, E, cellular elements (neutrophils, lymphocytes, macrophages), cytokines, lactoferrin, lysozyme, oligosaccharides, bifido- and lactobacteria, antioxidants and.
 The main class of human milk immunoglobulins is secretory immunoglobulin A (sIgA), which protects the surfaces of mucous membranes from the penetration of microorganisms, neutralizes toxins and localizes viruses, and stimulates phagocytosis. Currently, information on the local level of secretory immunoglobulin A in the development of the inflammatory process in the mammary gland is not numerous and requires research.
 The aim of the study. To assess the content of secretory IgA in breast milk of patients with lactational mastitis.
 Research metods. The study dealt with breast milk of 97 women aged 18 to 36 (average age: 26±5 years old). The standard indicators of the secretory immunoglobulin A contents in 30 practically healthy lactating women of the same age – the control group – were the issue of the analyses. The first group included 30 women with lactostasis, the second group consisted of 37 women with lactational mastitis. The content of secretory immunoglobulin A was determined by enzyme immunoassay using an automatic STAT FAX 303 plus analyzer.
 Results and discussion. The concentration of sIgA in breast milk with lactostasis is on average 0.72±0.04 mg/ml, which is 3 times higher than the control indicator (0.24±0.02 mg/ml; p<0.05). During the development of lactational mastitis, the level of sIgA is 0.75±0.05 mg/ml, which exceeds the control values by 3.1 times (р<0.05). The content of sIgA in the breast milk of women with lactostasis does not differ from the level of this immunoglobulin in patients with lactational mastitis. A high concentration of sIgA indicates the activation of immune protection on mucous membranes.
 Conclusions. Increased production of secretory immunoglobulin A in breast milk was found in experimental groups compared to practically healthy women, which indicates activation of local humoral immunity as a reaction to infection.

Human Milk Oligosaccharides And Site-Specific Glycosylation Heterogeneity Of Filipino Human Milk Glycoproteins Exhibit Dynamic Variations During Lactation As Influenced By Secretor Status And Coastal Environmental Condition – A Preliminary Study

Human Milk Oligosaccharides (HMOs) have a role in the immune system development of infants. HMOs and the N-glycans of human milk glycoproteins, especially highly fucosylated ones, function as prebiotics to the bifidogenic gut microbiota. This study reports the first longitudinal profile of HMOs and human milk glycoproteins from coastal, noncoastal, secretor and nonsecretor Filipino mothers analyzed and annotated using QTOF LC/MS and QqQ LC/MS - MRM, respectively. A milk glycan profile from coastal mothers revealed higher (P<0.05) presence of fucosylated branched HMOs, such as DFLNHa, LDFT, LNDFH I, and LNFP II. Moreover, secretor mothers expressed the highest 2’FL from colostrum (Day 5) until the end of the study (Month 6). Interestingly, the predominance of secretory IgA (64%) on the total milk glycoproteins from Filipino mothers supported their biological adaptation in conferring immune protection to their breastfeeding infant. Glycoform variations on milk glycoproteins, sIgA, IgG, Lactoferrin, and a1-Antitrypsin, in coastal mothers were observed. Moreover, lactoferrin was found to be highly glycosylated with 20 fucosylated and sialylated glycoforms. These results suggest that the coastal mother’s unique long-term seafood diet may have influenced their milk glycan profile and the potential incorporation of L-fucose derived from seafood in the biosynthesis of their milk glycans.

Factors associated with secretory IgA levels in colostrum and breastmilk

Background Secretory IgA (sIgA) content of breastmilk in the first postpartum month is a reflection of the pregnant woman's immune response to environmental antigen exposure. The role of secretory IgA in breastmilk is to protect and support the development of the neonatal immune response in early life.
 Objective To examine possible factors associated with sIgA levels in breastmilk and colostrum, including environmental exposure, food consumed, maternal history of atopy, and the appearance of allergic symptoms in infants. As a secondary objective, we determined the association between infant factors (IgE, exposure to cigarette smoke) and maternal factors (sIgA, maternal allergies) with infant allergies.
 Methods This prospective cohort study of 80 postpartum mothers and their infants was conducted at Sultan Agung Islamic Hospital, Semarang. We collected maternal colostrum on the second or third postpartum day and mature milk between the 22nd to 25th postpartum day. Exposure factors to mothers and infants in the final trimester of pregnancy up to one month postpartum was recorded through a questionnaire and home visits. The infant’s IgE level was measured at 4 months of age.
 Results Mean colostrum sIgA was 108.9 (SD 16.5) mg/dL (95%CI 97.9 to 121.1 mg/dL) and mean mature milk sIgA was 94.1 (SD 23.9) mg/dL (95%CI 89.1 to 99.2 mg/dL). Mean colostrum sIgA levels were higher in mothers exposed to cigarette smoke [119.1 (SD 1.7) vs. 92.9 (SD 1.5) mg/dL; P=0.026] and frequent infections [128.2 (SD 1.7) vs. 95.9 (SD 1.6) mg/dL; P=0.007] compared to that in unexposed mothers. Mean colostrum sIgA was also higher in mothers with atopic allergy than in those without (136.8 mg/dL vs. 99.3 mg/dL; p=0.017) and in mothers of infants with IgE levels >29 IU/ml than in mothers of infants with IgE levels <29 IU/mL (136.8 vs. 101.2 mg/mg/dL; P=0.045). Elevated colostrum sIgA (>136.8 mg/dL) was not associated with allergies in the infants (P=0.269).
 Conclusions Maternal atopic allergy and frequent infections are associated with increased colostrum sIgA levels. Breastmilk sIgA levels are not associated with allergies in the infant. Maternal exposure to antigens may stimulate the production of specific breastmilk sIgA.

The role of exclusive breastfeeding on sIgA and lactoferrin levels in toddlers suffering from Acute Respiratory Infection: A cross-sectional study

Secretion of Immunoglobulin A (sIgA) and lactoferrin is a nutrient content in breast milk that can increase immunity in preventing infectious diseases such as Acute Respiratory Infection (ARI). This research aims to determine the role of exclusive breastfeeding (EBF) on sIgA and Lactoferrin levels in toddlers suffering from ARI. A cross-sectional study was conducted on 124 toddlers under five from January–July 2021. Toddlers were selected using a purposive technique sampling from three Community Health Centers in Central Jakarta. Data were analyzed using t-test and ANOVA. The history of immunization, EBF, and frequency of ARI was significantly associated with levels of sIgA and lactoferrin. Parity only correlated with sIgA but not with lactoferrin levels. Maternal and toddlers' age, gender, and nutritional status were not significantly related to sIgA and lactoferrin levels. There is a significant (p-value <0.001) difference in the mean protein sIgA and lactoferrin levels in toddlers who were given EBF with ARI frequency <2 times and toddlers who were given EBF with ARI frequency ≥2 times. Toddlers who were exclusively breastfed with ARI frequency <2 times had higher levels of sIgA and lactoferrin (188901.77 pg/ml and 262.32 ng/ml, respectively) compared to infants given EBF with ARI frequency ≥2 times (136683.47 pg/ml and 181.49 ng/ml, respectively). History of immunization was also significantly (p-value <0.05) associated with levels of sIgA and lactoferrin in infants with ARI. The content of sIgA and lactoferrin in breast milk and immunization can increase the body's immune system in toddlers suffering from ARI.

Fecal secretory immunoglobulin a, human ß defensin-2, and calprotectin levels in preterm neonates who consumes breast milk only, formula milk only, and combination

Background: Secretory immunoglobulin A, human ß-defensin2 and calprotectin play an essential role in digestive system defense. This study aims to assess fecal SIgA, hBD-2, and calprotectin in preterm neonates (as inflammation marker) with different feeding patterns.&#x0D; Method: This study was cohort designed included 39 preterm neonates, which were categorized into breast milk only, formula milk only, and combination. Fecal SIgA, hBD-2, and calprotectin measured by ELISA.&#x0D; Results: Fecal SIga in the breast milk only group were significantly higher (p&lt;0.005). Fecal HBD-2 and calprotectin in the formula milk only group were highest but not significantly different (p=0.463) with the combination group.&#x0D; Conclusion: Fecal SIgA levels that consumed breast milk only were significantly higher. Fecal HBD-2 and calprotectin levels that consumed formula milk only were highest but not significantly different from the combination group.

Prevention of Atopic Dermatitis in Mice by Lactobacillus Reuteri Fn041 Through Induction of Regulatory T Cells and Modulation of the Gut Microbiota.

The development of atopic dermatitis (AD) in infants is closely related to the lagging development of intestinal microbiota, including that inoculated by breast milk bacteria, and immune development. Lactobacillus reuteri Fn041 is a secretory immunoglobulin A (sIgA) -coated bacterium derived from human milk. We intervene with L. reuteri Fn041 in maternal and offspring BALB/C mice during late gestation and lactation and after weaning of the pups, respectively. AD is then induced with MC903. L. reuteri Fn041 significantly suppresses AD symptoms such as skin swelling, mast cell, and eosinophil infiltration. This effect is attributed to the regulation of the systemic Th1 and Th2 cytokine ratios and the promotion of CD4+ CD25+ Foxp3+ regulatory T cell proliferation in mesenteric lymph nodes. It is also associated with the regulation of intestinal microbiota, particularly promoting Lactobacillus and Akkermansia. Our study strengthens the understanding that breast milk-derived sIgA coated potential probiotics are involved in the development of infant intestinal microbiota, thus promoting immune development and preventing allergic diseases, and expanding the knowledge of breast milk sIgA and bacterial interactions on infant immune development.

Optimization of a human milk\u2013directed quantitative sIgA ELISA method substantiated by mass spectrometry

Immunoglobulins are the primary protective products in human milk and are responsible for transferring maternal pathogen memory to the infant, providing protection by binding to recognized pathogens and inhibiting virulence. To better understand potentially protective/anti-infective compounds in human milk, the establishment of human milk–tailored analytical approaches is crucial, as most contemporary analytical methods have been optimized for plasma or serum. One of the most prominent immunoglobulins in human milk is secretory immunoglobulin A (sIgA), which may be relevant for the protection of breastfed infants from harmful pathogens. Advanced sIgA detection methods can help monitor the immune status and development of the mother-infant dyad. We therefore developed an enzyme-linked immunosorbent assay (ELISA) sIgA method for the quantitative analysis of IgA plus secretory component (SC), validated with sIgA standards and substantiated by mass spectrometry (MS)–based proteomics. A very strong correlation was observed between the MS-detected IgA1 and the human milk–specific sIgA ELISA (r = 0.82). Overall, the MS data indicate that the developed human milk sIgA ELISA does not differentiate between sIgA1 and sIgA2 and is, therefore, a reflection of total sIgA. Furthermore, our MS data and the human milk–derived sIgA ELISA data are better correlated than data derived from a standard serum IgA ELISA kit (relative to MS IgA1 r = 0.82 and r = 0.42, respectively). We therefore propose our human milk–specific sIgA ELISA as an ideal quantitative indicator of total sIgA with advantages over current serum IgA ELISA kits.

Six catalytic activities and cytotoxicity of immunoglobulin G and secretory immunoglobulin A from human milk

In the milk of healthy women, antibodies were found with different catalytic activities (abzymes), which are absent in the sera of other healthy people. Moreover, it was previously shown that DNase antibodies-abzymes of patients with autoimmune diseases are cytotoxic to cancer cells. In this work, it was first shown that IgG and secretory IgA (sIgA) do not possess embryotoxicity; they practically do not affect the development of fertilized eggs of sea urchins but demonstrate sperm toxicity. After addition to the eggs of sperm preincubated with IgG and sIgA, the number of unfertilized eggs was increased, in the case of sIgA 1.6-fold higher than that for IgG. The suppression of the growth of MCF-7 breast cancer cells by sIgA was 2.2 times more effective than with IgG antibodies. The relative enzymatic activity of milk sIgA was higher than IgG (-fold): 1.9 (DNase), 4.6 (amylase), 1.7 (peroxidase), 1.3 (protease), 3.7 [hydrolysis of poly(C)], 3.3 [hydrolysis of poly(U)], and 1.7 (oxidation of 3,3'-diaminobenzidine). One of the possible reasons for the observed difference between sIgA and IgG could be that all 6 catalytic activities of sIgA were, on average, 2.6 times higher than that for IgG. Correlation coefficients between all the relative 6 enzymatic activities of IgG and sIgA and their toxicity to sea urchin sperm and to cancer cells were calculated. Maximum correlation coefficients were observed for DNase (+0.71), protease (+0.64) activities for sIgA, as well as protease (+0.59) and RNase (+0.77) of IgG with their toxicity toward sperm. The correlation coefficients were also high between peroxidase activity (+0.85) of sIgA and poly(U) hydrolysis by IgG (+0.58) with their suppression of tumor cell growth. It has been suggested that the catalytic activities of abzymes may be important in the manifestation of their sperm toxicity and inhibition of cancer cell growth.

Robust and Specific Secretory IgA Against SARS-CoV-2 Detected in Human Milk.

SummaryThe SARS-CoV-2 immune response in human milk has not yet been examined, although protecting infants and young children from COVID-19 is critical for limiting community transmission and preventing serious illness and death. Here, milk samples from eight COVID-19-recovered and seven COVID-19-suspected donors were tested for antibody (Ab) binding to the SARS-CoV-2 Spike protein. All samples exhibited significant specific IgA reactivity to the full Spike, whereas 80% exhibited significant IgA and secretory (s)Ab binding to the Receptor-Binding Domain (RBD). Additionally, 67% samples exhibited IgG and/or IgM binding to RBD. IgA and sAb titers were highly correlated, indicating most IgA to be sIgA. Overall, these data indicate that a robust sIgA-dominant SARS-CoV-2 Ab response in human milk after infection should be expected in a significant majority of individuals. Further research is highly warranted to determine Ab functionality and the potential for exploiting extracted milk sIgA for therapeutic use.

Evaluation of Cross-Protection between G1a- and G2a-Genotype Porcine Epidemic Diarrhea Viruses in Suckling Piglets.

Simple SummaryPorcine epidemic diarrhea (PED), caused by PED virus (PEDV), is a devastating enteric disease in pigs worldwide. At least two genotypes (G1 and G2) and five subgenotypes (G1a, G1b, G2a, G2b, andG2c) of PEDV strains have been identified. To date, the reports on the antigenicity and immunogenicity of those viruses are limited and the results documented on cross-neutralization among different genotypes and/or subgenotypes of PEDV were inconsistent. This study aimed to observe the comparative pathogenicity and cross-protection between G1a and G2a PEDVs, and thus find a new insight into the antigenicity and immunogenicity of PEDVs. The results of the present study demonstrated that the G2a-based inactivated vaccine could provide sterilizing immunity against both highly virulent homologous and heterologous PEDV challenges. In contrast, the G1a-based inactivated vaccine could induce a sterilizing immune response against challenge of homologous strain CV777 and only provide partial protection for the challenge of a heterologous G2a PEDV CH/JX/01. The findings of this study might explain the underlying mechanism that severe PED and deaths still occurred among the neonatal piglets of which CV777-based PEDV vaccine were administered in China, and imply G2a-based PEDV vaccine used in this study might be a good vaccine candidate for PEDV which may provide solid protection against circulating highly virulent PEDVs.To date, two genotypes, i.e., genotype 1 (G1) and genotype 2 (G2), of porcine epidemic diarrhea virus (PEDV) have been identified in swine, while the cross protection between the G2a and G1a subgenotypes is undetermined. Hence, in the present study, we attempted to observe a comparative pathogenicity and cross protection of G1a (CV777) and G2a (CH/JX/01) PEDVs. Initially pregnant sows were vaccinated twice with the two kinds of inactivated G1a- and G2a-based PEDV vaccines, respectively and the delivered neonatal piglets were challenged with prototype isolates of G1a and G2a PEDVs, and then the pathogenicity and cross-protection in neonatal piglets were observed. The results showed that CH/JX/01, a highly virulent and dominant G2a PEDV strain currently circulating in China had more severe pathogenicity in vitro and in vivo, and induced more strong immune responses, including higher titers of sIgA in maternal milk than that induced by CV777 PEDV, a prototype of G1a PEDV strain. All piglets from the sows immunized with CH/JX/01 could not only survive when challenged with the homologous PEDV, but also be fully protected when challenged with heterogenous G1a PEDV. In contrast, the piglets from the sows immunized with CV777 could be protected when challenged with homologous PEDV and only partially protected when challenged with heterologous G2a strain of PEDV (CH/JX/01). The findings of this study provide new insights into the pathogenicity, antigenicity, and immunogenicity of currently circulating wild type G2a PEDV, which might be valuable for the development of novel PEDV vaccine candidates with improved efficacy.

Safety and immunogenicity of an investigational maternal trivalent group B streptococcus vaccine in pregnant women and their infants: Results from a randomized placebo-controlled phase II trial

BackgroundThis study evaluated the safety and immunogenicity of an investigational trivalent group B streptococcus (GBS) vaccine in US pregnant women, transplacental serotype-specific antibody transfer and persistence in infants, and serotype-specific antibodies in breast milk. MethodsThis randomized, observer-blind, placebo-controlled trial administered one dose of trivalent GBS vaccine (n = 49) or placebo (n = 26) to healthy pregnant 18–40-year-old women at 240/7–346/7 weeks’ gestation. Women were enrolled from March 2014 to August 2015. Safety follow-up continued through postpartum day 180. Primary immunogenicity objectives were to evaluate serotype Ia/Ib/III-specific immunoglobulin G (IgG) levels in sera from women on day 1 (pre-vaccination), day 31, delivery and postpartum days 42 and 90, and from infants at birth (cord blood), days 42 and 90. Antibody transfer ratios (cord blood/maternal sera at delivery) and serotype-specific secretory immunoglobulin A (sIgA) and IgG in breast milk after delivery and on postpartum days 42 and 90 were evaluated. The planned sample size was not based on statistical assumptions for this descriptive study. ResultsBaseline characteristics were similar between groups. Serious adverse events were reported for 16% of GBS-vaccinated women and 15% of their infants, and 15% of placebo recipients and 12% of their infants; none were fatal or deemed vaccine-related. Serotype-specific IgG geometric mean concentrations (GMCs) were 13–23-fold higher in vaccine vs placebo recipients on day 31 and persisted until postpartum day 90. Median antibody concentrations were substantially higher in women with detectable pre-vaccination antibody concentrations. Antibody transfer ratios in the vaccine group were 0.62–0.82. Infant IgG GMCs and breast milk sIgA GMCs were higher in the vaccine vs the placebo group at all timepoints. ConclusionsMaternal immunization with the trivalent GBS vaccine in US women had a favorable safety profile, elicited antibodies that were transplacentally transferred and persisted in infants for a minimum of 3 months. Clinical trial registrationClinicaltrials.gov, NCT02046148

Impact of Breast Milk Secretory Immunoglobulin A on Infants Acute Gastroenteritis

BACKGROUND: Acute gastroenteritis is one of the most common infections in childhood and it can be especially dangerous in the first 6 months of life with a higher risk of moderate and severe dehydration, especially in infants who are not exclusively breastfed. Secretory immunoglobulin A (sIgA) is the first line of defense on the intestinal epithelium from pathogenic microorganisms and intestinal toxins.&#x0D; AIM: The aim of this study was to determine whether breast milk sIgA has some protective effect on the intestinal epithelium as well as on the severity and duration of the clinical signs in infants with acute gastroenteritis depending on the type of nutrition.&#x0D; MATERIALS AND METHODS: A total of 23 infants with acute gastroenteritis divided into two groups based on the feeding patterns (type of milk) were included in the study. Investigated indicators were severity of symptoms, dehydration degree, and the need for parenteral rehydration.&#x0D; RESULTS: We identified a statistically significant association between group affiliation and the sIgA levels in stool between the first and the second groups (p = 0.001346). The most common cause of acute gastroenteritis in infants was Rotavirus. Our study has shown that exclusive breastfeeding reduces the risk of Rotavirus infection, especially in the first 6 months of life, OR = 0.0758, 95% confidence interval (CI) (0.0071–0.8074).&#x0D; CONCLUSION: The presence of breast milk sIgA in infants has an effect on the severity of the clinical picture of acute gastroenteritis by reducing the frequency of vomiting, the number and severity of diarrheal episodes, the risk of moderate and severe dehydration, and fever frequency.

Role of Breastfeeding and Onset of Atopic Dermatitis in Children Patient: a Cross Sectional Study

Abstract: Atopic dermatitis (AD) is a multifactorial belongs to the burden disease in childhood. It needs to be prevented to reach their optimal growth. Exclusive breastfeeding given during the first six months of life provides nutritional benefits and is thought to protect children from allergic or infectious diseases, such as AD. This study aims to determine the relationship between breastfeeding and onset of atopic dermatitis. This was an observational analytic study using cross-sectional method. Samples were taken consecutively at the Dermatovenereology Polyclinic of referral hospital and Puskesmas in Medan. This study included all pediatric patients aged 6 months to <18 years diagnosed with AD and were interviewed with informed consent. Children who didn’t get breastmilk were excluded. There result was a significant relationship between breastfeeding (exclusively to partially) and AD onset. There was no relationship between breastfeeding (exclusively to prelacteally) and AD onset. Polyunsaturated fatty acids, sIgA, and TGF-β2 in the breast milk of mothers with atopy is lower than mothers without atopy. Breastfeeding exclusively has a protective effect on AD. Further research is needed to analyzes various factors by comparing genetic predisposition.

Sequence characterization and N-glycoproteomics of secretory immunoglobulin A from donkey milk

Secretory immunoglobulin A (sIgA) is the major antibody present in the human milk where it confers passive immunity to neonates. Other than human, non-ruminants such as equine, swine etc., also possess sIgA in milk but detailed characterization is limited. In the present study, we characterized sIgA from donkey milk for amino acid sequence and N-glycosylation through LC-MS/MS analysis. The complete amino acid sequence of alpha chain constant region (CH) was elucidated. The sequence analysis of variable regions (VH and VL) and light chain constant region (CL) showed several amino acid substitutions indicating the presence of diverse immunoglobulin repertoire. Glycoproteomic analysis of secretory component revealed bi-antennary complex and hybrid types with differential core fucosylation at site N83LT, only complex glycans at N135GT, N423GT and N530LT with mainly NeuAc whereas N291QT harbors high mannose glycans. Heavy chain possesses majorly bi-antennary complex with differential core fucosylation at sites N139AS and N338VS, in which N338VS shows partial occupancy. Joining chain harbors only complex type at N72IS, with core fucosylation and terminal NeuGc to some extent. N-glycan repertoire in part is similar to human sIgA. This comprehensive analysis of sequence and glycan pattern of donkey milk sIgA would be beneficial for its potential applications.

The Association Between Breast Milk Group B Streptococcal Capsular Antibody Levels and Late-onset Disease in Young Infants.

Animal-model studies have demonstrated less group B streptococcal (GBS) invasive disease and gastrointestinal colonization after enteral administration of serotype-specific capsular antibodies. There is, however, a paucity of information on the association of breast milk GBS serotype-specific capsular antibodies and risks for invasive disease in infants. The aim of this study was to explore the association between natural secretory immunoglobulin A (sIgA) capsular antibodies in breast milk and the occurrence of late-onset disease (LOD) in young infants. A matched case-control study was undertaken in infants <3 months of age in Johannesburg, South Africa. Breast milk samples were collected on cases and controls matched for gestational age, maternal age, and human immunodeficiency virus status at time of enrollment. Capsular serotype Ia, Ib, III, and V sIgA antibody concentrations were measured using the fluorescence-based micro-bead immunosorbent assay. Breast milk samples were available for 31 LOD cases (8 serotype Ia and 23 serotype III), 21 recto-vaginally colonized matched controls (10 serotype Ia and 11 serotype III), and 84 serotype Ia and 105 serotype III noncolonized matched controls. Using a Bayesian model to estimate the probability of disease, there were 90% reductions in the risks of developing serotypes Ia and III LOD with sIgA concentrations ≥0.14 µg/mL and ≥2.52 µg/mL, respectively. Breast milk sIgA capsular antibodies were associated with lower risks for LOD in young infants. The ability of GBS polysaccharide-protein conjugate vaccines currently under development to induce sIgA responses warrant investigation as potential mediators of protection against LOD.