{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T05:17:46Z","timestamp":1784438266923,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011109","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000}}],"reference-count":78,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T00:00:00Z","timestamp":1699315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Thomas F. and Kate Miller Jeffress Memorial Trust and Bank of America","award":["Jeffress Trust Award in Interdisciplinary Research and Jeffress Trust Award Program in Research Advancing Health"],"award-info":[{"award-number":["Jeffress Trust Award in Interdisciplinary Research and Jeffress Trust Award Program in Research Advancing Health"]}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T32-GM145443"],"award-info":[{"award-number":["T32-GM145443"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Transplacental antibody transfer is crucially important in shaping neonatal immunity. Recently, prenatal maternal immunization has been employed to boost pathogen-specific immunoglobulin G (IgG) transfer to the fetus. Multiple factors have been implicated in antibody transfer, but how these key regulators work together to elicit selective transfer is pertinent to engineering vaccines for mothers to optimally immunize their newborns. Here, we present the first quantitative mechanistic model to uncover the determinants of placental antibody transfer and inform personalized immunization approaches. We identified placental Fc\u03b3RIIb expressed by endothelial cells as a limiting factor in receptor-mediated transfer, which plays a key role in promoting preferential transport of subclasses IgG1, IgG3, and IgG4, but not IgG2. Integrated computational modeling and <jats:italic>in vitro<\/jats:italic> experiments reveal that IgG subclass abundance, Fc receptor (FcR) binding affinity, and FcR abundance in syncytiotrophoblasts and endothelial cells contribute to inter-subclass competition and potentially inter- and intra-patient antibody transfer heterogeneity. We developed an <jats:italic>in silico<\/jats:italic> prenatal vaccine testbed by combining a computational model of maternal vaccination with this placental transfer model using the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine as a case study. Model simulations unveiled precision prenatal immunization opportunities that account for a patient\u2019s anticipated gestational length, placental size, and FcR expression by modulating vaccine timing, dosage, and adjuvant. This computational approach provides new perspectives on the dynamics of maternal-fetal antibody transfer in humans and potential avenues to optimize prenatal vaccinations that promote neonatal immunity.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011109","type":"journal-article","created":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T18:32:42Z","timestamp":1699381962000},"page":"e1011109","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Quantitative mechanistic model reveals key determinants of placental IgG transfer and informs prenatal immunization strategies"],"prefix":"10.1371","volume":"19","author":[{"given":"Remziye E.","family":"Wessel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0226-0933","authenticated-orcid":true,"given":"Sepideh","family":"Dolatshahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,11,7]]},"reference":[{"issue":"31","key":"pcbi.1011109.ref001","doi-asserted-by":"crossref","first-page":"3886","DOI":"10.1016\/j.vaccine.2014.05.008","article-title":"Challenges in vaccination of neonates, infants and young children","volume":"32","author":"ME Pichichero","year":"2014","journal-title":"Vaccine"},{"issue":"5","key":"pcbi.1011109.ref002","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.cell.2018.06.045","article-title":"Stereotypic Immune System Development in Newborn Children","volume":"174","author":"A Olin","year":"2018","journal-title":"Cell"},{"key":"pcbi.1011109.ref003","article-title":"Requirement for a betal 2-microglobulin-associated Fc receptor for acquisition of maternal IgG by fetal and neonatal mice","author":"E Simister","year":"1995"},{"key":"pcbi.1011109.ref004","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fimmu.2015.00077","article-title":"Understanding the ontogeny of the immune system to promote immune-mediated health for life","volume":"6","author":"A Marchant","year":"2015","journal-title":"Front Immunol"},{"issue":"7473","key":"pcbi.1011109.ref005","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/S0140-6736(66)92190-8","article-title":"THE TRANSMISSION OF IMMUNITY FROM MOTHER TO YOUNG AND THE CATABOLISM OF IMMUNOGLOBULINS","volume":"288","author":"FW Brambell","year":"1966","journal-title":"Lancet"},{"key":"pcbi.1011109.ref006","article-title":"Factors affecting the FcRn-mediated transplacental transfer of antibodies and implications for vaccination in pregnancy","author":"CR Wilcox","year":"2017","journal-title":"Front Immunol"},{"key":"pcbi.1011109.ref007","article-title":"Placental transport of immunoglobulin G","author":"NE Simister","year":"2003","journal-title":"Vaccine"},{"key":"pcbi.1011109.ref008","article-title":"Specificity and affinity of human Fc receptors and their polymorphic variants for human IgG subclasses","author":"P Bruhns","year":"2009"},{"issue":"Pt 2","key":"pcbi.1011109.ref009","first-page":"297","article-title":"Ontogeny and distribution of Fc gamma receptors in the human placenta. 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