Maternal gatekeepers: How maternal antibody Fc characteristics influence passive transfer and infant protection

Langel, Stephanie N.; Otero, Claire E.; Martinez, David R.; Permar, Sallie R.

doi:10.1371/journal.ppat.1008303

Cited by 22 publications

(20 citation statements)

References 52 publications

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“…Equally, IgA Fc region characteristics may determine IgA passive transfer or effector function in breast milk (Goonatilleke et al, 2019;Langel et al, 2020;Steffen et al, 2020). Of note, the glycosylation pattern of IgA antibodies is more complex, extensive and diverse; IgA2 is found at a higher percentage in mucosal secretions and has a great number of conserved N-glycans compared to IgA1, which dominates in serum (Mattu et al, 1998).…”

Section: Factors Affecting Maternal Antibody Transfer In Breast Milkmentioning

confidence: 99%

“…Furthermore, the blunting effect noted has not been comprehensively defined, with a gap in our understanding of the impact of maternal antibody on qualitative or functional infant humoral immunity. Pre-existing antibodies have been shown to induce higher affinity humoral responses, possibly explained by competitive binding in the germinal center (GC) and/or a boost in uptake and antigen presentation, mediated by immune complexes in a Fc glycosylation-dependent manner (Zhang et al, 2013;Lofano et al, 2018;Garg et al, 2019;Langel et al, 2020). Most recently, a randomized control trial in Thailand (NCT02408926) studied term infants who were immunized with either acellular (aP)-or whole cell (wP) pertussis vaccines in infancy; results showed that infants born to women vaccinated in pregnancy had reduced pertussis-specific titres.…”

Section: Once Transferred What Do We Know About the Effect Of Maternmentioning

confidence: 99%

“…In contrast to other blunting theories, a recent study by Vono et al (2019) showed that maternal antibodies do not prevent neonatal B-cell activation but exert their influence by limiting the expansion of T-follicular helper cells, thereby shaping GC output, i.e., B-cell differentiation into effective plasma cells and/or memory cells, and the antigenspecific B-cell repertoire (Vono et al, 2019). Interestingly, at low or intermediate titres, maternal antibodies did not prevent the induction of memory-cells, suggesting a gradient effect on infant immune responses (Vono et al, 2019;Langel et al, 2020).…”

Section: Systemic Infant Cellular Immunitymentioning

confidence: 99%

“…removing the glycans from IgG2b has previously eliminated its immunosuppressive activity both in vitro and in vivo (Langel et al, 2020).…”

Section: Vaccine Factorsmentioning

confidence: 99%

“…Modifying vaccine-type, dosing (single vs. multiple), delivery route and adjuvant formulation (to stimulate different Toll-like receptors) can selectively modify the Fc domain and induce glycan combinations which confer desired antibody effector functions ( Selman et al, 2012 ; Mahan et al, 2014 , 2016 ; Francica et al, 2017 ; Lofano et al, 2018 ). For example, removing the glycans from IgG2b has previously eliminated its immunosuppressive activity both in vitro and in vivo ( Langel et al, 2020 ).…”

Section: The Bigger Picture: What Else Influences the Mother/infant Dmentioning

confidence: 99%

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Maternal Immunization: Nature Meets Nurture

Saso

Kampmann

2020

Front. Microbiol.

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Vaccinating women in pregnancy (i.e., maternal immunization) has emerged as a promising tool to tackle infant morbidity and mortality worldwide. This approach nurtures a 'gift of nature,' whereby antibody is transferred from mother to fetus transplacentally during pregnancy, or postnatally in breast milk, thereby providing passive, antigenspecific protection against infections in the first few months of life, a period of increased immune vulnerability for the infant. In this review, we briefly summarize the rationale for maternal immunization programs and the landscape of vaccines currently in use or in the pipeline. We then direct the focus to the underlying biological phenomena, including the main mechanisms by which maternally derived antibody is transferred efficiently to the infant, at the placental interface or in breast milk; important research models and methodological approaches to interrogate these processes, particularly in the context of recent advances in systems vaccinology; the potential biological and clinical impact of high maternal antibody titres on neonatal ontogeny and subsequent infant vaccine responses; and key vaccine-and host-related factors influencing the maternal-infant dyad across different environments. Finally, we outline important gaps in knowledge and suggest future avenues of research on this topic, proposing potential strategies to ensure optimal testing, delivery and implementation of maternal vaccination programs worldwide.

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Section: Factors Affecting Maternal Antibody Transfer In Breast Milkmentioning

confidence: 99%

Section: Once Transferred What Do We Know About the Effect Of Maternmentioning

confidence: 99%

Section: Systemic Infant Cellular Immunitymentioning

confidence: 99%

“…removing the glycans from IgG2b has previously eliminated its immunosuppressive activity both in vitro and in vivo (Langel et al, 2020).…”

Section: Vaccine Factorsmentioning

confidence: 99%

Section: The Bigger Picture: What Else Influences the Mother/infant Dmentioning

confidence: 99%

See 3 more Smart Citations

Maternal Immunization: Nature Meets Nurture

Saso

Kampmann

2020

Front. Microbiol.

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Humoral Immune Response in SARS-CoV-2 Infection and Its Therapeutic Relevance

Portilho

Gaspar

Gaspari

2022

Frontiers of COVID-19

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Compromised SARS-CoV-2-specific placental antibody transfer

Atyeo

Pullen

Bordt

et al. 2021

Cell

197

193

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SARS-CoV-2 infection causes more severe disease in pregnant women compared to age-matched non-pregnant women. Whether maternal infection causes changes in the transfer of immunity to infants remains unclear. Maternal infections have previously been associated with compromised placental antibody transfer, but the mechanism underlying this compromised transfer is not established. Here, we used systems serology to characterize the Fc-profile of influenza-, pertussis-, and SARS-CoV-2-specific antibodies transferred across the placenta. Influenza- and pertussis-specific antibodies were actively transferred. However, SARS-CoV-2-specific antibody transfer was significantly reduced compared to influenza- and pertussis-specific antibodies, and cord titers and functional activity were lower than in maternal plasma. This effect was only observed in third trimester infection. SARS-CoV-2-specific transfer was linked to altered SARS-CoV-2-antibody glycosylation profiles and was partially rescued by infection-induced increases in IgG and increased FCGR3A placental expression. These results point to unexpected compensatory mechanisms to boost immunity in neonates, providing insights for maternal vaccine design.

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Maternal gatekeepers: How maternal antibody Fc characteristics influence passive transfer and infant protection

Cited by 22 publications

References 52 publications

Maternal Immunization: Nature Meets Nurture

Maternal Immunization: Nature Meets Nurture

Humoral Immune Response in SARS-CoV-2 Infection and Its Therapeutic Relevance

Compromised SARS-CoV-2-specific placental antibody transfer

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