Update on Transplacental Transfer of IgG Subclasses: Impact of Maternal and Fetal Factors

Clements, Toby; Rice, Thomas F.; Vamvakas, George; Barnett, Sara; Barnes, Megan; Donaldson, Beverly; Jones, Christine E; Kampmann, Beate; Holder, Beth

doi:10.3389/fimmu.2020.01920

Cited by 101 publications

(104 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IgG1, IgG3, or IgG4 transferred better than IgG2, except for S. pneumoniae , for which IgG2 transfer was significantly higher. This was unexpected as classically it has been described that the greatest transport occurs for IgG1, followed by IgG4, IgG3, and finally IgG2 ( 20 ), although a recent report showed a different hierarchy of subclass transfer and identified a number of other studies that also observed different transfer efficiencies, depending on the antigen tested ( 21 ). However, IgG1 levels were the highest for almost all antigens in cord blood, probably because of the overall higher levels of this IgG subclass in maternal blood.…”

Section: Discussionmentioning

confidence: 86%

“…Only IgG is transferred across the placenta with the highest rate occurring during the third trimester of pregnancy ( 17 ), although some studies suggest that maternal IgE may also be transferred to the fetus as IgG/IgE complexes ( 18 ). IgG subclasses have different affinities for the FcRn receptor leading to differences in the efficiency of transfer ( 19 ); classically it was stated that the greatest transport occurs for IgG1, followed by IgG4, IgG3, and finally IgG2 ( 20 ), although a recent update on transplacental transfer of IgG subclasses showed that it is different depending on the antigen and study populations ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Reduced Placental Transfer of Antibodies Against a Wide Range of Microbial and Vaccine Antigens in HIV-Infected Women in Mozambique

et al. 2021

View full text Add to dashboard Cite

Transplacental transfer of antibodies is essential for conferring protection in newborns against infectious diseases. We assessed the impact of different factors, including gestational age and maternal infections such as HIV and malaria, on the efficiency of cord blood levels and placental transfer of IgG subclasses. We measured total IgG and IgG subclasses by quantitative suspension array technology against 14 pathogens and vaccine antigens, including targets of maternal immunization, in 341 delivering HIV-uninfected and HIV-infected mother-infant pairs from southern Mozambique. We analyzed the association of maternal HIV infection, Plasmodium falciparum exposure, maternal variables and pregnancy outcomes on cord antibody levels and transplacental transfer. Our results show that maternal antibody levels were the main determinant of cord antibody levels. Univariable and multivariable analysis showed that HIV reduced the placental transfer and cord levels of IgG and IgG1 principally, but also IgG2 to half of the antigens tested. P. falciparum exposure and prematurity were negatively associated with cord antibody levels and placental transfer, but this was antigen-subclass dependent. Our findings suggest that lower maternally transferred antibodies may underlie increased susceptibility to infections of HIV-exposed infants. This could affect efficacy of maternal vaccination, especially in sub-Saharan Africa, where there is a high prevalence of HIV, malaria and unfavorable environmental factors.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Reduced Placental Transfer of Antibodies Against a Wide Range of Microbial and Vaccine Antigens in HIV-Infected Women in Mozambique

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In addition to the role of antibodies in binding and neutralization, antibodies contribute to protection against COVID-19 disease through their ability to recruit the innate immune response with their Fc-domain (18,19). The Fc-functions of the humoral immune response play a critical role in resolution of , are associated with protection from infection following vaccination (21), play a critical role in antibody transfer across the placenta (22)(23)(24)(25) and may also influence transfer into breastmilk (26). To define qualitative features of the vaccine-induced humoral immune response across pregnancy and early life, here we comprehensively profiled the humoral immune response following mRNA vaccination in pregnant, lactating, or non-pregnant women who received the Pfizer/BioNTech or the Moderna vaccine.…”

Section: Introductionmentioning

confidence: 99%

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

Atyeo

DeRiso

Davis

et al. 2021

Preprint

View full text Add to dashboard Cite

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.

show abstract

“…Interestingly, though IgG1-4 can all be detected in fetal circulation, there is an especially high quantity of IgG1. Data support a general transfer hierarchy of IgG subclasses, which is believed to be IgG1 > IgG4 > IgG3 > IgG2, although deviation from this hierarchy in regard to IgG2, IgG3, and IgG4 transport has been reported across study populations [ 23 , 60 , 61 , 62 ]. As one might expect, binding between FcRn and IgG is critical to this transfer: a recombinant H435A-bearing IgG1 with undetectable affinity for human FcRn exhibited a ~90% reduction in transfer rate ex vivo [ 63 ].…”

Section: Fcrn Expression and Its Effects On Homeostatic Igg Distrimentioning

confidence: 78%

In Translation: FcRn across the Therapeutic Spectrum

Cao

2021

IJMS

View full text Add to dashboard Cite

As an essential modulator of IgG disposition, the neonatal Fc receptor (FcRn) governs the pharmacokinetics and functions many therapeutic modalities. In this review, we thoroughly reexamine the hitherto elucidated biological and thermodynamic properties of FcRn to provide context for our assessment of more recent advances, which covers antigen-binding fragment (Fab) determinants of FcRn affinity, transgenic preclinical models, and FcRn targeting as an immune-complex (IC)-clearing strategy. We further comment on therapeutic antibodies authorized for treating SARS-CoV-2 (bamlanivimab, casirivimab, and imdevimab) and evaluate their potential to saturate FcRn-mediated recycling. Finally, we discuss modeling and simulation studies that probe the quantitative relationship between in vivo IgG persistence and in vitro FcRn binding, emphasizing the importance of endosomal transit parameters.

show abstract

Update on Transplacental Transfer of IgG Subclasses: Impact of Maternal and Fetal Factors

Abstract: information regarding levels and transfer of IgG subclasses in healthy term pregnancies and demonstrates the importance of recording detailed clinical information in studies of antibody transfer, including parity, ethnicity, and timing of maternal vaccine delivery.

Cited by 101 publications

References 37 publications

Reduced Placental Transfer of Antibodies Against a Wide Range of Microbial and Vaccine Antigens in HIV-Infected Women in Mozambique

Reduced Placental Transfer of Antibodies Against a Wide Range of Microbial and Vaccine Antigens in HIV-Infected Women in Mozambique

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

In Translation: FcRn across the Therapeutic Spectrum

Contact Info

Product

Resources

About