Pregnancy enables antibody protection against intracellular infection

Erickson, John J.; Archer-Hartmann, Stephanie; Yarawsky, Alexander E; Miller, Jeanette L.C.; Seveau, Stéphanie; Shao, Tzu-Yu; Severance, Ashley L.; Miller-Handley, Hilary; Wu, Yuehong; Pham, Giang; Wasik, Brian R.; Parrish, Colin R.; Hu, Yueh Chiang; Lau, Joseph T.Y.; Azadi, Parastoo; Herr, Andrew B.; Way, Sing Sing

doi:10.1038/s41586-022-04816-9

Cited by 30 publications

(20 citation statements)

References 57 publications

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“…The consequence of reduced IL-10 production is suboptimal protective T-cell responses to intracellular Listeria infection in the neonate. Taken together, studies by Rizzuto et al 6 and Erickson et al 8 underscore a common theme that the exposed sialic acid residues on trophoblast-derived antigens or IgG generated during pregnancy may exquisitely titrate the levels of B cell and CD4 + T-cell activation.…”

mentioning

confidence: 85%

Sugar-coated Antigens Generated During Pregnancy Mediate Fetomaternal Tolerance

Sayin

Durgam²,

Chong³

2022

Transplantation

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mentioning

confidence: 85%

Sugar-coated Antigens Generated During Pregnancy Mediate Fetomaternal Tolerance

Sayin

Durgam²,

Chong³

2022

Transplantation

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“…Transgenerational transmission of immunity is seen in invertebrates and vertebrates. In mammals this involves antibody provisioning via transplacental transfer and breastfeeding (Atyeo & Alter, 2021; Clements et al, 2020; Erickson, 2022), maternal microchimerism, and antigen exposure in utero, phenomena termed “transgenerational immune priming” (Blackwell, in prep; Roth et al, 2018). These mechanisms suggest that there is widespread selection for pathogen defenses that learn about specific pathogens and transmit this information to offspring.…”

Section: The Behavioral Immune System Includes Constitutive and Induc...mentioning

confidence: 99%

Homo medicus: The transition to meat eating increased pathogen pressure and the use of pharmacological plants in Homo

Hagen

Blackwell

Lightner

et al. 2023

American Journal of Biological Anthropology

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The human lineage transitioned to a more carnivorous niche 2.6 mya and evolved a large body size and slower life history, which likely increased zoonotic pathogen pressure. Evidence for this increase includes increased zoonotic infections in modern hunter‐gatherers and bushmeat hunters, exceptionally low stomach pH compared to other primates, and divergence in immune‐related genes. These all point to change, and probably intensification, in the infectious disease environment of Homo compared to earlier hominins and other apes. At the same time, the brain, an organ in which immune responses are constrained, began to triple in size. We propose that the combination of increased zoonotic pathogen pressure and the challenges of defending a large brain and body from pathogens in a long‐lived mammal, selected for intensification of the plant‐based self‐medication strategies already in place in apes and other primates. In support, there is evidence of medicinal plant use by hominins in the middle Paleolithic, and all cultures today have sophisticated, plant‐based medical systems, add spices to food, and regularly consume psychoactive plant substances that are harmful to helminths and other pathogens. We propose that the computational challenges of discovering effective plant‐based treatments, the consequent ability to consume more energy‐rich animal foods, and the reduced reliance on energetically‐costly immune responses helped select for increased cognitive abilities and unique exchange relationships in Homo. In the story of human evolution, which has long emphasized hunting skills, medical skills had an equal role to play.

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“…While vaccine-induced RBD IgG1 drives functions across the maternal-fetal dyad (Figure 4C, D), post-translational antibody glycosylation appears to contribute more to potency in the fetus than the pregnant individual (Figure 5, 6, 7B, 7C, Supplemental Figure 7 and 8). All polyclonal IgG have N-linked glycans on the Fc domain that drive Fcg receptors binding and effector functions (38,39,54,88)and 20% of the population have additional modifications on the Fab domain (93,94) that have the potential to impact stability, half-life and avidity to antigens (59,61,95). Subtle differences between maternal and cord IgG glycosylation have been reported (87,96).…”

Section: Differential Glycosylation Contributes To Antibody Functiona...mentioning

confidence: 99%

“…Our data show that these same glycans are altered on cord and not maternal RBD IgG with vaccination (Figure 5 and Supplemental Figure 7) , impacting RBD ADNKA potency in the newborn (Figure 6). Recent data in a mouse model of Listeria infection show that vaccination during as compared to before pregnancy induces Fab domain sialylation that enhances protection for pups (61). Whether pregnancy-specific changes in antibody glycosylation could similarly improve infant protection against COVID-19 is not known.…”

Section: Differential Glycosylation Contributes To Antibody Functiona...mentioning

confidence: 99%

“…Moreover, antibody functional potency, breadth and coordination between neutralizing and Fc effector responses likely contribute to protection (26,(53)(54)(55)(56)(57). Some data demonstrate that maternal immune adaptation to pregnancy alters antibody subclass and glycosylation (30,(58)(59)(60)(61)(62)(63)(64)(65), but the implications for antibody functions and what exists for the fetus are only just beginning to be appreciated (66)(67)(68)(69)(70).…”

Section: Introductionmentioning

confidence: 99%

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Diverging maternal and infant cord antibody functions from SARS-CoV-2 infection and vaccination in pregnancy

Adhikari

Kang

et al. 2023

Preprint

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Immunization in pregnancy is a critical tool that can be leveraged to protect the infant with an immature immune system but how vaccine-induced antibodies transfer to the placenta and protect the maternal-fetal dyad remains unclear. Here, we compare matched maternal-infant cord blood from individuals who in pregnancy received mRNA COVID-19 vaccine, were infected by SARS-CoV-2, or had the combination of these two immune exposures. We find that some but not all antibody neutralizing activities and Fc effector functions are enriched with vaccination compared to infection. Preferential transport to the fetus of Fc functions and not neutralization is observed. Immunization compared to infection enriches IgG1-mediated antibody functions with changes in antibody post-translational sialylation and fucosylation that impact fetal more than maternal antibody functional potency. Thus, vaccine enhanced antibody functional magnitude, potency and breadth in the fetus are driven more by antibody glycosylation and Fc effector functions compared to maternal responses, highlighting prenatal opportunities to safeguard newborns as SARS-CoV-2 becomes endemic.

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Pregnancy enables antibody protection against intracellular infection

Cited by 30 publications

References 57 publications

Sugar-coated Antigens Generated During Pregnancy Mediate Fetomaternal Tolerance

Sugar-coated Antigens Generated During Pregnancy Mediate Fetomaternal Tolerance

Homo medicus: The transition to meat eating increased pathogen pressure and the use of pharmacological plants in Homo

Diverging maternal and infant cord antibody functions from SARS-CoV-2 infection and vaccination in pregnancy

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