Active free secretory component and secretory IgA in human milk: do maternal vaccination, allergy, infection, mode of delivery, nutrition and active lifestyle change their concentrations?

BACKGROUND: Free secretory component (free SC) in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion, but its concentration in human milk is unknown. To evaluate the relationship between free SC and SIgA, the influence of maternal factors (vaccination during pregnancy, allergy, previous infections, nutrition, mode of delivery and active lifestyle) on the concentrations of those secretory immune components in human milk was investigated. METHODS: Concentration of active free SC and SIgA in 124 milk samples from 91 mothers were measured via ELISA. RESULTS: Free SC in milk from Tdap-vaccinated mothers was lower than the Tdap-flu-vaccinated, flu-vaccinated or Rhogam-vaccinated mothers. Free SC in mothers who had a cesarean delivery was higher than mothers who had a vaginal delivery. Free SC in the nonallergic group was higher than the allergic group. Free SC was higher in mothers who rarely/never eat junk food, than in mothers who always/frequently eat junk food. Free SC also was higher in the moderate exercise group (active lifestyle) compared with the group who rarely/never exercise (sedentary lifestyle). Free SC in human milk was not affected by previous maternal infection or probiotic supplementation whereas SIgA was not changed by all investigated maternal factors. CONCLUSION: This study suggests that active free SC is more impacted by maternal factors than active SIgA in human milk. IMPACT: Active free secretory component (free SC) is more impacted by maternal factors than active secretory IgA (SIgA) in human milk. Vaccination during pregnancy, allergy, nutrition, type of delivery and active lifestyle affect the secretion of free SC in human milk, but not SIgA secretion. Free SC in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion against pathogens and its active concentration in milk strongly varies between mothers, partially due to their specific maternal background.

Receptor-binding Domain Severe Acute Respiratory Syndrome Coronavirus 2-specific Antibodies in Human Milk From Mothers With Coronavirus Disease 2019 Polymerase Chain Reaction or With Symptoms Suggestive of Coronavirus Disease 2019.

ABSTRACT: This study aims to compare the receptor-binding domain (RBD) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody titers in human milk between mothers with a confirmed coronavirus disease 2019 (COVID-19) polymerase chain reaction (PCR) test and mothers with viral symptoms suggestive of COVID-19. The area under the curve (AUC) for RBD SARS-CoV-2-specific secretory immunoglobulin A (SIgA)/immunoglobulin A (IgA), secretory immunoglobulin M (SIgM)/immunoglobulin M (IgM), immunoglobulin G (IgG), and free secretory components (fSC) in milk samples from eight mothers with a confirmed COVID-19 PCR, eight mothers with viral symptoms (no PCR testing), and six unexposed mothers (pre-pandemic 2018). AUCs of RBD SARS-CoV-2-specific SIgA/IgA, SIgM/IgM, IgG, and fSC in milk samples were comparable between mothers with confirmed COVID-19 PCR and mothers with viral symptoms of suggestive COVID-19. AUCs of RBD-specific SIgA/IgA, IgG, and fSC were higher in the COVID-19-exposed group than in the unexposed group, and SIgM/IgM tended to be higher in the exposed mothers. In conclusion, women with viral symptoms suggestive of COVID-19 could secrete antibodies and fSC specific to SARS-CoV-2 in human milk.

Human Milk Antibodies Against S1 and S2 Subunits from SARS-CoV-2, HCoV-OC43, and HCoV-229E in Mothers with A Confirmed COVID-19 PCR, Viral SYMPTOMS, and Unexposed Mothers.

BACKGROUND: Preexisting immunity to SARS-CoV-2 could be related to cross-reactive antibodies to common human-coronaviruses (HCoVs). This study aimed to evaluate whether human milk antibodies against to S1 and S2 subunits SARS-CoV-2 are cross-reactive to S1 and S2 subunits HCoV-OC43 and HCoV-229E in mothers with a confirmed COVID-19 PCR test, in mothers with previous viral symptoms during COVID-19 pandemic, and in unexposed mothers; Methods: The levels of secretory IgA (SIgA)/IgA, secretory IgM (SIgM)/IgM, and IgG specific to S1 and S2 SARS-CoV-2, and reactive to S1 + S2 HCoV-OC43, and HCoV-229E were measured in milk from 7 mothers with a confirmed COVID-19 PCR test, 20 mothers with viral symptoms, and unexposed mothers (6 Ctl1-2018 and 16 Ctl2-2018) using ELISA; Results: The S2 SARS-CoV-2 IgG levels were higher in the COVID-19 PCR (p = 0.014) and viral symptom (p = 0.040) groups than in the Ctl1-2018 group. We detected a higher number of positive correlations between the antigens and secretory antibodies in the COVID-19 PCR group than in the viral symptom and Ctl-2018 groups. S1 + S2 HCoV-OC43-reactive IgG was higher in the COVID-19 group than in the control group (p = 0.002) but did not differ for the other antibodies; Conclusions: Mothers with a confirmed COVID-19 PCR and mothers with previous viral symptoms had preexisting human milk antibodies against S2 subunit SARS-CoV-2. Human milk IgG were more specific to S2 subunit SARS-CoV-2 than other antibodies, whereas SIgA and SIgM were polyreactive and cross-reactive to S1 or S2 subunit SARS-CoV-2.

Influenza Vaccine Associated with the Gene Expression of T Cell Surface Markers in Human Milk.

Background: The function of neonatal T cells is reduced compared to adult T cells. T cells could be transferred to the infants through human milk and compensate for their immature T cells. As the subsets of T cells present in human milk have been incompletely described, this study investigated the association between the maternal factors (influenza vaccine, maternal age, and lactation time), the gene expression of T cell surface markers (cluster of differentiation [CD] and chemokine receptors [CCR]), and the concentrations of T cell-related cytokines in human milk. Materials and Methods: The gene expressions of T cell markers and the concentrations of T cell-related cytokines were determined in milk samples from 16 women. Eight donors received influenza vaccine, and eight were not vaccinated during 2019-2020 for the flu season 2020. Results: For T cell surface markers, the gene expression of CD8A was higher than CD4, CCR6, CD25, CXCR5, CD62L, and CD44 in human milk. CD44 copy gene was lower than CCR7 and CXCR3, while CD4 copy gene was lower than CXCR3 in human milk. Women with influenza vaccine had higher copy genes of CD44, CD8A, CD62L, and CD25 and lower CCR7 copy gene in milk than in women without influenza vaccine. Interleukin-17 concentration in human milk decreased with increasing lactation time. Gene expression of T cell markers and cytokine concentrations varied between lactating women. Conclusions: Although a larger study is needed, it appears that the influenza vaccine is associated with the gene expression of T cell markers in human milk.

Comparison of Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibodies' Binding Capacity Between Human Milk and Serum from Coronavirus Disease 2019-Recovered Women.

Background: Human milk from coronavirus disease 2019 (COVID-19)-recovered women may be useful as oral antibody therapy to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and provide long-term immunity to neonates and young children. As convalescent plasma is already used as antibody therapy, this study aimed to compare the binding capacity of antibodies specific to the receptor-binding domain (RBD) of SARS-CoV-2 between human milk and serum from COVID-19-recovered women. Materials and Methods: The areas under the curve (AUCs) for IgA, IgM, and IgG specific to the SARS-CoV-2 RBD in human milk and serum samples were measured using enzyme-linked immunosorbent assay. Milk samples were collected from 12 COVID-19-recovered women, while serum samples were from 10 COVID-19-recovered women. The antibody concentrations were also determined. Results: Our study reveals that SARS-CoV-2 RBD-specific antibody titers differed between human milk and serum samples from COVID-19-recovered women. When the AUCs were not divided by the antibody concentration, SARS-CoV-2 RBD-specific IgA, IgM, and IgG levels were higher in the serum sample group than the human milk group (p < 0.001). However, the titers of SARS-CoV-2 RBD-specific IgM (AUC/µg of IgM) and IgG (AUC/µg of IgG) were higher in human milk samples than serum samples (p < 0.05). The titer of SARS-CoV-2 RBD-specific IgA (AUC/mg of IgA) was higher in the serum sample group than the human milk group (p < 0.01). Conclusions: Human milk antibodies specific to the RBD of SARS-CoV-2 must be purified to obtain comparable binding capacity observed with SARS-CoV-2 RBD-specific serum antibodies.

Previous viral symptoms and individual mothers influenced the leveled duration of human milk antibodies cross-reactive to S1 and S2 subunits from SARS-CoV-2, HCoV-229E, and HCoV-OC43.

OBJECTIVE: The influence of previous viral symptoms on the level and duration of human milk antibodies reactive to SARS-CoV-2, and common human coronaviruses (HCoVs) was investigated. STUDY DESIGN: Antibodies reactive to S1 and S2 subunits from SARS-CoV-2, HCoV-OC43, and HCoV-229E were measured via ELISA in human milk samples collected from March to June 2020 in mothers with and without viral symptoms. RESULTS: The presence of viral symptoms influenced the levels of SARS-CoV-2 S2-reactive SIgA/IgA and tended to influence SARS-CoV-2 S1 SIgA/IgA and S2-reactive SIgM/IgM in human milk but did not relate to IgG. HCoV-229E S1 + S2-reactive SIgA/IgA and SIgM/IgM, as well as HCoV-OC43 S1 + S2-reactive IgG were related to the symptoms. The duration of antibody levels in human milk in mothers with viral symptoms varied between 3 and 4 months post maternal report of viral symptoms. CONCLUSION: Previous viral symptoms and individual mothers may change the antibody cross-reactive levels to SARS-CoV-2 and HCoVs in human milk.

The effects of probiotic supplementation on the gene expressions of immune cell surface markers and levels of antibodies and pro-inflammatory cytokines in human milk.

OBJECTIVE: This study investigated the impact of probiotic supplementation on the gene expressions of cluster of differentiation (CD) as cell markers and the concentrations of antibodies and cytokines in human milk. STUDY DESIGN: Gene expressions of CD28, CD19, and CD38 were determined in milk from 15 women ingesting daily probiotics (from Greek yogurt) and 12 women who do not consume probiotics. Concentrations of antibodies and cytokines were measured using ELISA. RESULTS: Gene expression of CD28 tended to be higher in milk from mothers ingesting daily probiotics than mothers who did not take probiotics. Interleukin-6 (IL-6) concentration in milk was higher in mothers ingesting probiotics than those who do not consume probiotics. The increase of IL-6 level in human milk was positively correlated with total IgA and IgG concentrations. CONCLUSIONS: Probiotic supplementation could enhance the secretion of IL-6 in human milk. Human milk IL-6 may improve neonatal immunity due to its stimulation of total IgA and IgG.

Complete Genome Sequences of Mycobacterium smegmatis Phages NihilNomen and Carlyle, Isolated in Las Vegas, Nevada.

We present the complete genomes of the Mycobacterium smegmatis phages Carlyle and NihilNomen, isolated from soil in Las Vegas, Nevada. The phages were isolated and annotated by undergraduate students enrolled in the Phage Discovery course offered by the School of Life Sciences at the University of Nevada Las Vegas.