Induction of SARS-CoV-2-Specific IgG and IgA in Serum and Milk with Different SARS-CoV-2 Vaccines in Breastfeeding Women: A Cross-Sectional Study in Northern Spain

Lechosa-Muñiz, Carolina; Paz-Zulueta, María; Méndez-Legaza, José Manuel; Irure‐Ventura, Juan; González, Rocío; Montes, Jorge; López-Hoyos, Marcos; Llorca, Javier; Cabero-Pérez, María Jesús

doi:10.3390/ijerph18168831

Cited by 105 publications

(54 citation statements)

References 20 publications

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“…In the breastmilk, detection of neutralizing antibody and increase in inhibitory capability was notable 7 days after dose 2, corresponding with the peak levels of SARS-CoV-2 RBD-specific antibody isotypes, especially IgG1, and IgA levels at this point. These findings are concordant with previously reported increases in breastmilk SARS-CoV-2-specific IgA and IgG levels within a week after the second vaccine dose ( 10 , 11 , 27 , 28 ). SARS-CoV-2 specific IgA in the breastmilk reportedly achieved maximal levels a week after the second dose, where SARS-CoV-2-specific IgG was only evident 1 week after the second dose ( 12 , 14 , 28 – 31 ).…”

Section: Discussionsupporting

confidence: 93%

Neutralizing Activity and SARS-CoV-2 Vaccine mRNA Persistence in Serum and Breastmilk After BNT162b2 Vaccination in Lactating Women

et al. 2022

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BackgroundThere is limited information on the functional neutralizing capabilities of breastmilk SARS-CoV-2-specific antibodies and the potential adulteration of breastmilk with vaccine mRNA after SARS-CoV-2 mRNA vaccination.MethodsWe conducted a prospective cohort study of lactating healthcare workers who received the BNT162b2 vaccine and their infants. The presence of SARS-CoV-2 neutralizing antibodies, antibody isotypes (IgG, IgA, IgM) and intact mRNA in serum and breastmilk was evaluated at multiple time points using a surrogate neutralizing assay, ELISA, and PCR, over a 6 week period of the two-dose vaccination given 21 days apart.ResultsThirty-five lactating mothers, median age 34 years (IQR 32-36), were included. All had detectable neutralizing antibodies in the serum immediately before dose 2, with significant increase in neutralizing antibody levels 7 days after this dose [median 168.4 IU/ml (IQR 100.7-288.5) compared to 2753.0 IU/ml (IQR 1627.0-4712.0), p <0.001]. Through the two vaccine doses, all mothers had detectable IgG1, IgA and IgM isotypes in their serum, with a notable increase in all three antibody isotypes after dose 2, especially IgG1 levels. Neutralizing antibodies were detected in majority of breastmilk samples a week after dose 2 [median 13.4 IU/ml (IQR 7.0-28.7)], with persistence of these antibodies up to 3 weeks after. Post the second vaccine dose, all (35/35, 100%) mothers had detectable breastmilk SARS-CoV-2 spike RBD-specific IgG1 and IgA antibody and 32/35 (88.6%) mothers with IgM. Transient, low intact vaccine mRNA levels was detected in 20/74 (27%) serum samples from 21 mothers, and 5/309 (2%) breastmilk samples from 4 mothers within 1 weeks of vaccine dose. Five infants, median age 8 months (IQR 7-16), were also recruited - none had detectable neutralizing antibodies or vaccine mRNA in their serum.ConclusionMajority of lactating mothers had detectable SARS-CoV-2 antibody isotypes and neutralizing antibodies in serum and breastmilk, especially after dose 2 of BNT162b2 vaccination. Transient, low levels of vaccine mRNA were detected in the serum of vaccinated mothers with occasional transfer to their breastmilk, but we did not detect evidence of infant sensitization. Importantly, the presence of breastmilk neutralising antibodies likely provides a foundation for passive immunisation of the breastmilk-fed infant.

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Section: Discussionsupporting

confidence: 93%

Neutralizing Activity and SARS-CoV-2 Vaccine mRNA Persistence in Serum and Breastmilk After BNT162b2 Vaccination in Lactating Women

et al. 2022

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“…Thus far, we identified ten published studies on the immune response to an mRNA-based COVID-19 vaccine in breastmilk of lactating women [9][10][11][12][13][14][15][16][17][18] . Our study adds new information on the vaccine-induced immune response: we show neutralizing ability of antibodies in milk against spike and 4 VOCs that is IgG-driven and high levels of IFNγ in milk.…”

Section: Discussionmentioning

confidence: 99%

“…As of September 28, 2021, we identified ten published studies on the immune response to an mRNA-based COVID-19 vaccine in breastmilk of lactating women [9][10][11][12][13][14][15][16][17][18] . The number of lactating women included in eight of these studies ranged between 5 and 31; two remaining studies included 84 and 110 lactating women 17,18 . All studies measured levels of SARS-CoV-2specific IgA, IgG, and in some cases SARS-CoV-2-specific IgM.…”

Section: Introductionmentioning

confidence: 99%

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

Narayanaswamy

Pentecost

Schoen

et al. 2021

Preprint

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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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“…SARS-CoV-2-specific antibody responses are engendered in human milk after vaccination with Pfizer/BioNTech's BNT162b2 (also known as Comirnaty; INN: tozinameran) [1], as well as Moderna's mRNA-1273 [2]. Both of these mRNA vaccines encode a humancodon-optimized SARS-CoV-2 spike glycoprotein, using the first described Wuhan-Hu-1 strain as the basis for design, together with proline substitutions at lysine 986 and valine 987 to stabilize the prefusion intermediate.…”

Section: Introductionmentioning

confidence: 99%

Human Milk Antibodies after BNT162b2 Vaccination Exhibit Reduced Binding against SARS-CoV-2 Variants of Concern

Low

et al. 2022

Vaccines

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SARS-CoV-2-specific antibody responses are engendered in human milk after BNT162b2 vaccination. However, the emergence of variants of concern (VOCs) raises concerns about the specificity of and potential cross-protection mediated by milk antibody responses, which are crucial for passive immunity transferred from breastfeeding mothers to their infants. In this study, we collected milk samples at three different time points pre- and post-vaccination, and measured milk IgA antibody binding to the receptor binding domain (RBD) of the original Wuhan-Hu-1 strain, and the four VOCs, namely Alpha, Beta, Gamma and Delta. We report a significant level of anti-RBD IgA in milk collected at 4–6 weeks after the second dose of vaccination compared to pre-vaccination. We observed around a 30% reduction in binding to most VOCs, including the major circulating Delta variant, compared to the original Wuhan-Hu-1 strain. As COVID-19 vaccines may take some time to be approved for infants, these individuals remain at risk for severe disease and rely mainly on transferred passive immunity. Our findings support the current recommendations for vaccinating lactating women with the aim of transferring mucosal immunity to breastfeeding infants.

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Induction of SARS-CoV-2-Specific IgG and IgA in Serum and Milk with Different SARS-CoV-2 Vaccines in Breastfeeding Women: A Cross-Sectional Study in Northern Spain

Cited by 105 publications

References 20 publications

Neutralizing Activity and SARS-CoV-2 Vaccine mRNA Persistence in Serum and Breastmilk After BNT162b2 Vaccination in Lactating Women

Neutralizing Activity and SARS-CoV-2 Vaccine mRNA Persistence in Serum and Breastmilk After BNT162b2 Vaccination in Lactating Women

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

Human Milk Antibodies after BNT162b2 Vaccination Exhibit Reduced Binding against SARS-CoV-2 Variants of Concern

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