The multifaceted roles of breast milk antibodies

Atyeo, Caroline; Alter, Galit

doi:10.1016/j.cell.2021.02.031

Cited by 128 publications

(136 citation statements)

References 194 publications

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“…Whereas, breastmilk contained exclusively low titers of spike-reactive IgA, circulating anti-spike antibodies spanned from low to high titers and through IgG, IgA, and IgM isotypes. These results highlight the functional compartmentalization between mucosal and the systemic immunity and the limitations of systemic administered BNT162b2 vaccine in eliciting a strong mucosal response 54 . The function of antibodies produced within the mammary gland MALT is to provide protective immunity to the suckling infant through the secretion of polymeric antibodies complexed to jchain and secretory component proteins 13 .…”

Section: Discussionmentioning

confidence: 80%

Non-neutralizing secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon BNT162b2 vaccination

Gonçalves

Charepe

et al. 2021

Preprint

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In view of data scarcity to guide decision-making in breastfeeding women, we evaluated how mRNA vaccines impact immune response of lactating health care workers (HCW) and the effector profile of breast milk transferred immune protection. We show that upon BNT162b2 vaccination, immune transfer via milk to suckling infants occurs through secretory IgA (SIgA) and T cells. Functionally, spike-SIgA was non-neutralizing and its titers were unaffected by vaccine boosting, indicating that spike-SIgA is produced in a T-cell independent manner by mammary gland. Even though their milk was devoid of neutralizing antibodies, we found that lactating women had higher frequencies of RBD-reactive circulating memory B cells and more RBD-IgG antibodies, when compared to controls. Nonetheless, blood neutralization titers in lactating and non-lactating HCW were similar. Further studies are required to determine transferred antibodies and spike-T cells complete functional profile and whether they can mediate protection in the suckling infant.HighlightsMilk and blood responses to BNT162b2 vaccine are initially isotype discordantImmune transfer via milk to suckling infants occurs by spike-reactive SIgA and T cellsSpike-reactive SIgA in the breastmilk is non-neutralizing and T-cell independentLactating vs non-lactating HCW had distinct cellular responses, despite similar NT50

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Section: Discussionmentioning

confidence: 80%

Non-neutralizing secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon BNT162b2 vaccination

Gonçalves

Charepe

et al. 2021

Preprint

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“…Collectively, these data emphasize that while the breast clearly enriches IgM and IgA delivery to the breastmilk (30,31),vaccination appears to dramatically augment highly functional IgG transit to the milk that are likely key to antiviral immunity across viral pathogens (31).…”

Section: Optimal Vaccine-induced Antibody Transfer To the Breastmilk Requires Boostingmentioning

confidence: 89%

COVID-19 mRNA vaccines drive differential Fc-functional profiles in pregnant, lactating, and non-pregnant women

Atyeo

DeRiso

Davis

et al. 2021

Preprint

Self Cite

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Significant immunological changes occur throughout pregnancy to tolerize the mother and allow growth of the fetal graft. However, additional local and systemic immunological adaptations also occur, allowing the maternal immune system to continue to protect the dyad against foreign invaders both during pregnancy and after birth through lactation. This fine balance of tolerance and immunity, along with physiological and hormonal changes, contribute to increased susceptibility to particular infections in pregnancy, including more severe COVID-19 disease. Whether these changes also make pregnant women less responsive to vaccination or induce altered immune responses to vaccination remains incompletely understood. To holistically define potential changes in vaccine response during pregnancy and lactation, we deeply profiled the humoral vaccine response in a group of pregnant and lactating women and non-pregnant age-matched controls. Vaccine-specific titers were comparable, albeit slightly lower, between pregnant and lactating women, compared to non-pregnant controls. Among pregnant women, we found higher antibody titers and functions in those vaccinated with the Moderna vaccine. FcR-binding and antibody effector functions were induced with delayed kinetics in both pregnant and lactating women compared to non-pregnant women. Antibody boosting resulted in high FcR-binding titers in breastmilk. These data point to an immune resistance to generate highly inflammatory antibodies during pregnancy and lactation, and a critical need to follow prime/boost timelines in this vulnerable population to ensure full immunity is attained.

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“…Lactating women who have recovered from respiratory virus infections produce antibodies in human milk that can neutralize offending viruses in vivo 1 . The production of protective antibodies in human milk after influenza vaccination in lactating women confers local mucosal immunity to infants and has informed antenatal vaccination programs for diseases such as influenza and pertussis in lactating women 2 , 3 .…”

Section: Introductionmentioning

confidence: 99%

Codominant IgG and IgA expression with minimal vaccine mRNA in milk of BNT162b2 vaccinees

Low

et al. 2021

npj Vaccines

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Lactating women can produce protective antibodies in their milk after vaccination, which has informed antenatal vaccination programs for diseases such as influenza and pertussis. However, whether SARS-CoV-2-specific antibodies are produced in human milk as a result of COVID-19 vaccination is still unclear. In this study, we show that lactating mothers who received the BNT162b2 vaccine secreted SARS-CoV-2-specific IgA and IgG antibodies into milk, with the most significant increase at 3–7 days post-dose 2. Virus-specific IgG titers were stable out to 4–6 weeks after dose 2. In contrast, SARS-CoV-2-specific IgA levels showed substantial decay. Vaccine mRNA was detected in few milk samples (maximum of 2 ng/ml), indicative of minimal transfer. Additionally, infants who consumed post-vaccination human milk had no reported adverse effects up to 28 days post-ingestion. Our results define the safety and efficacy profiles of the vaccine in this demographic and provide initial evidence for protective immunity conferred by milk-borne SARS-CoV-2-specific antibodies. Taken together, our study supports recommendations for uninterrupted breastfeeding subsequent to mRNA vaccination against COVID-19.

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The multifaceted roles of breast milk antibodies

Cited by 128 publications

References 194 publications

Non-neutralizing secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon BNT162b2 vaccination

Non-neutralizing secretory IgA and T cells targeting SARS-CoV-2 spike protein are transferred to the breastmilk upon BNT162b2 vaccination

COVID-19 mRNA vaccines drive differential Fc-functional profiles in pregnant, lactating, and non-pregnant women

Codominant IgG and IgA expression with minimal vaccine mRNA in milk of BNT162b2 vaccinees

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