Humoral and Cell-Mediated Immune Response in Colostrum from Women Diagnosed Positive for SARS-CoV-2

Narayanaswamy, Vignesh; Pentecost, Brian T.; Alfandari, Dominique; Chin, Emily; Minor, Kathleen; Kastrinakis, Alyssa; Lieberman, Tanya; Arcaro, Kathleen F.; Leftwich, Heidi

doi:10.1089/bfm.2021.0082

Cited by 17 publications

(27 citation statements)

References 38 publications

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“…Subsequent steps followed the protocol for detection of RBD-specific immunoglobulins. 19 The neutralization assay was performed using a V-PLEX SARS-CoV-2 Panel 6 multiplex assay by Mesoscale Discovery (K15436U). The assay quantitatively measures antibodies in the sample that can inhibit the interaction of spike and its variants with ACE2.…”

Section: Methodsmentioning

confidence: 99%

Neutralizing Antibodies and Cytokines in Breast Milk After Coronavirus Disease 2019 (COVID-19) mRNA Vaccination

Narayanaswamy

Pentecost

Schoen

et al. 2021

Obstetrics &Amp; Gynecology

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OBJECTIVE: To evaluate immune responses to coronavirus disease 2019 (COVID-19) mRNA-based vaccines present in breast milk and transfer of the immune responses to breastfeeding infants. METHODS: We enrolled 30 lactating women who received mRNA-based COVID-19 vaccines from January through April 2021 in this cohort study. Women provided serial milk samples, including milk expressed before vaccination, across 2–3 weeks after the first dose, and across 3 weeks after the second dose. Women provided their blood, spotted on cards (dried blood spots), 19 days after the first dose and 21 days after the second dose. Stool samples from the breastfed infants were collected 21 days after mothers' second vaccination. Prepandemic samples of milk, dried blood spots, and infant stool were used as controls. Milk, dried blood spots, and infant stool were tested by enzyme-linked immunosorbent assay for receptor-binding domain (RBD)–specific immunoglobulin (Ig)A and IgG. Milk samples were tested for the presence of neutralizing antibodies against the spike and four variants of concern: D614G, Alpha (B.1.1.7), Beta (B.1.351), and Gamma (P.1). Levels of 10 cytokines were measured in milk samples. RESULTS: Milk from COVID-19-immunized women neutralized the spike and four variants of concern, primarily driven by anti-RBD IgG. The immune response in milk also included significant elevation of interferon-γ. The immune response to maternal vaccination was reflected in breastfed infants: anti-RBD IgG and anti-RBD IgA were detected in 33% and 30% of infant stool samples, respectively. Levels of anti-RBD antibodies in infant stool correlated with maternal vaccine side effects. Median antibody levels against RBD were below the positive cutoffs in prepandemic milk and infant stool samples. CONCLUSION: Humoral and cellular immune responses to mRNA-based COVID-19 vaccination are present in most women’s breast milk. The milk anti-RBD antibodies can neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike and variants of concern. Anti-RBD antibodies are transferred to breastfed infants, with the potential to confer passive immunity against SARS-CoV-2.

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Section: Methodsmentioning

confidence: 99%

Neutralizing Antibodies and Cytokines in Breast Milk After Coronavirus Disease 2019 (COVID-19) mRNA Vaccination

Narayanaswamy

Pentecost

Schoen

et al. 2021

Obstetrics &Amp; Gynecology

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“…On average, the proportion of sIgA1 in the milk proteins of COVID-19 colostrum was 8.6 times greater than in the Ctrl colostrum (Figure 2D), thus indicating that the mothers’ responses to the infection and additional adaptive immunological protection for the infants from viruses may be introduced through the gastrointestinal or respiratory tract. Indeed, it has been reported that a portion of sIgA present in milk from COVID-19 patients were RBD-specific 53,54 . Such protection may be further strengthened by other adaptive immunity-related proteins that appear in higher abundances in COVID-19 colostrum than in Ctrl colostrum (Figure 2F).…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of human milk reveals nutritional and immune benefits in the colostrum from mothers with COVID-19

Guo¹,

Tan

Zhu

et al. 2022

Preprint

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The range of benefits breastfeeding provides neonates and infants include nutrition, improved neonatal survival, and reduced morbidity from certain diseases. It also aids maternal health by speeding postpartum recovery. However, due to concern about the risk of SARS-CoV-2 transmission and the lack of evidence of breastmilk's protective effects against the virus, whether mothers with COVID-19 should be encouraged to breastfeed is under debate. Here, we present the results of proteomic and glycoproteomic studies of breast milk (colostrum and mature milk) from mothers with confirmed COVID-19. All colostrum samples exhibited significantly upregulated immune-related proteins, especially whey proteins with antiviral properties against SARS-CoV-2, and increased glycosylation levels and heterogeneity at those proteins. Such adaptive differences in milk from COVID-19 mothers tend to fade in mature milk from the same mothers one month postpartum. These results suggest the immune benefits of colostrum from mothers with COVID-19 and provide molecular-level insights that aid breastmilk feeding decisions in cases of active infection.

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“…In a disease state where SARS-CoV-2 is mucosally-acquired, we and others find the immune response mounted is primarily IgA 19,[24][25][26][27] . This is seen for one of the three vaccinated women in our study who also previously tested positive for SARS-CoV-2.…”

Section: Covid-19 Mrna Immunization In Milk From Lactating Womenmentioning

confidence: 92%

“…The copyright holder for this preprint this version posted October 14, 2021. ; https://doi.org/10.1101/2021.10.12.21264890 doi: medRxiv preprint COVID-19 mRNA immunization in milk from lactating women 10 Levels of SARS-CoV-2 RBD-specific immunoglobulins were measured as previously described 19 . For detection of total immunoglobulins, 96-well plates were coated with anti-IgA (α-chain specific) or anti-IgG (H+L specific) capture antibodies at 1 μg/mL (Jackson ImmunoResearch Laboratories, Inc.).…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 99%

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Breastfeeding infants receive neutralizing antibodies and cytokines from mothers immunized with a COVID-19 mRNA vaccine

Narayanaswamy

Pentecost

Schoen

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Objective: To evaluate the immune response to COVID-19 mRNA-based vaccines present in breastmilk and the transfer of the immune response to the breastfeeding child. Methods: A prospective cohort study enrolled 30 lactating women who received an mRNA-based COVID-19 vaccine between January and April 2021. Women provided serial milk samples, which included milk expressed before vaccination, milk expressed across 2-3 weeks after the first dose, and milk expressed across 3 weeks after the second dose. Women also were asked to provide their blood, spotted on cards (dried blood spots; DBS) 19 days after the first dose and 21 days after the second dose. Stool samples from the breastfed infants were collected 21 days after mothers received their second dose. Pre-pandemic samples of milk, DBS cards, and infant stool from prior studies were also utilized. Milk and infant stool samples were tested by ELISA for receptor-binding domain (RBD)-specific IgA and IgG. Milk samples were tested for the presence of neutralizing antibodies against the spike and four variants of concern (VOCs): D614G, B.1.1.7 (alpha), B.1.351 (beta), and P.1 (gamma). Milk samples were also tested by electrochemiluminescence assay for levels of 10 cytokines. Results: Milk from COVID-19-immunized women neutralized the spike and four VOCs and this response is primarily IgG-driven. The immune response in milk also included significantly elevated levels of interferon-γ (IFN-γ). The immune response to maternal vaccination was reflected in breastfed babies; anti-RBD IgG and anti-RBD IgA was detected in 33% and 30% of infant stool samples, respectively. Levels of anti-RBD antibodies in infant stool correlated with maternal vaccine side-effects. Conclusion: Humoral and cellular immune responses to mRNA-based COVID-19 vaccination are present in the breastmilk of most women. The milk anti-RBD antibodies can neutralize SARS-CoV-2 spike and VOCs. Importantly, we describe for the first time the transfer of anti-RBD antibodies to breastfed infants, with the potential to confer passive immunity against SARS-CoV-2

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Humoral and Cell-Mediated Immune Response in Colostrum from Women Diagnosed Positive for SARS-CoV-2

Cited by 17 publications

References 38 publications

Neutralizing Antibodies and Cytokines in Breast Milk After Coronavirus Disease 2019 (COVID-19) mRNA Vaccination

Neutralizing Antibodies and Cytokines in Breast Milk After Coronavirus Disease 2019 (COVID-19) mRNA Vaccination

Proteomic analysis of human milk reveals nutritional and immune benefits in the colostrum from mothers with COVID-19

Breastfeeding infants receive neutralizing antibodies and cytokines from mothers immunized with a COVID-19 mRNA vaccine

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