{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:38:58Z","timestamp":1782949138497,"version":"3.54.5"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013408","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000}}],"reference-count":117,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1U19AI145825"],"award-info":[{"award-number":["1U19AI145825"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI186995"],"award-info":[{"award-number":["1R01AI186995"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA 023108-41"],"award-info":[{"award-number":["P30 CA 023108-41"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P20-GM113132"],"award-info":[{"award-number":["P20-GM113132"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Maternal antibodies serve as a temporary form of inherited immunity, providing humoral protection to vulnerable neonates. Whereas IgG is actively transferred up a concentration gradient via the neonatal Fc Receptor (FcRn), maternal IgA and IgM are typically excluded from fetal circulation. Further, not all IgG molecules exhibit the same transfer efficiency, being influenced by subclass, Fab and Fc domain glycosylation, antigen-specificity, and the temporal dynamics of maternal antibody responses. Here, we investigate the phenotypes and functions of maternal and cord blood antibodies induced by SARS-CoV-2 infection and compare them to those induced by mRNA vaccination, focusing on breadth of antigen recognition and antiviral functions including neutralization and effector function. While cord blood coronavirus-specific antibody functional breadth and potency appeared to be more compromised than binding breadth and potency in both groups, vaccination induced substantially greater function and breadth in cord blood than did natural infection. These functional phenotypes were associated with speciation of the maternal serum repertoires, as some IgG subpopulations were enriched while others were relatively depleted from cord blood. Relevant to the continued protection of vulnerable infants in the context of a diversifying pathogen, key observations included the greater breadth of antibody effector functions as compared to neutralization, which was associated with greater affinity for antigen and the more efficient placental transfer of IgG subclasses with better affinity to Fc receptors. This work provides new insights into the binding and functional breadth of inherited antibody responses that are likely responsible for the protection of infants born to seropositive mothers from severe SARS-CoV-2 infection despite continued viral diversification.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013408","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T17:41:37Z","timestamp":1754502097000},"page":"e1013408","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Patterns and functional consequences of antibody speciation in maternal-fetal transfer of coronavirus-specific humoral immunity"],"prefix":"10.1371","volume":"21","author":[{"given":"Andrew P.","family":"Hederman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah M.","family":"Brookes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harini","family":"Natarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Heyndrickx","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin K.","family":"Ari\u00ebn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Weiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amihai","family":"Rottenstreich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gila","family":"Zarbiv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tessa","family":"Goetghebuer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Marchant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4253-3476","authenticated-orcid":true,"given":"Margaret E.","family":"Ackerman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"issue":"18","key":"ppat.1013408.ref001","doi-asserted-by":"crossref","first-page":"493","DOI":"10.15585\/mmwr.mm7218a4","article-title":"COVID-19 Mortality Update - United States, 2022","volume":"72","author":"FB Ahmad","year":"2023","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"6","key":"ppat.1013408.ref002","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.cell.2020.10.052","article-title":"Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality","volume":"183","author":"T Zohar","year":"2020","journal-title":"Cell"},{"issue":"11","key":"ppat.1013408.ref003","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1038\/s41591-021-01540-1","article-title":"Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 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Wang","year":"2021","journal-title":"Nature"},{"issue":"7855","key":"ppat.1013408.ref010","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/s41586-021-03324-6","article-title":"mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants","volume":"592","author":"Z Wang","year":"2021","journal-title":"Nature"},{"issue":"9","key":"ppat.1013408.ref011","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1016\/j.cell.2021.02.037","article-title":"Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera","volume":"184","author":"D Zhou","year":"2021","journal-title":"Cell"},{"issue":"24","key":"ppat.1013408.ref012","doi-asserted-by":"crossref","first-page":"2273","DOI":"10.1056\/NEJMoa2104983","article-title":"Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons","volume":"384","author":"TT Shimabukuro","year":"2021","journal-title":"N Engl J 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transplacental transport of human IgG antibodies","volume":"117","author":"S Borghi","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"49","key":"ppat.1013408.ref032","doi-asserted-by":"crossref","first-page":"18709","DOI":"10.1073\/pnas.0606304103","article-title":"Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies","volume":"103","author":"C Vaccaro","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"ppat.1013408.ref033","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1093\/intimm\/13.8.993","article-title":"The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of gamma-globulin in humans","volume":"13","author":"M Firan","year":"2001","journal-title":"Int Immunol"},{"issue":"12","key":"ppat.1013408.ref034","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/S0167-5699(97)01172-9","article-title":"FcRn: the MHC 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(SARS-CoV-2) Infection","volume":"138","author":"NT Joseph","year":"2021","journal-title":"Obstet Gynecol"},{"issue":"3","key":"ppat.1013408.ref038","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2020.12.027","article-title":"Compromised SARS-CoV-2-specific placental antibody transfer","volume":"184","author":"C Atyeo","year":"2021","journal-title":"Cell"},{"issue":"6","key":"ppat.1013408.ref039","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1001\/jamapediatrics.2021.0038","article-title":"Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios","volume":"175","author":"DD Flannery","year":"2021","journal-title":"JAMA Pediatr"},{"issue":"3","key":"ppat.1013408.ref040","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1001\/jamapediatrics.2021.5683","article-title":"Maternal and Neonatal SARS-CoV-2 Immunoglobulin G Antibody Levels at Delivery After Receipt of the BNT162b2 Messenger RNA COVID-19 Vaccine During the Second Trimester of Pregnancy","volume":"176","author":"N Kugelman","year":"2022","journal-title":"JAMA Pediatr"},{"issue":"2","key":"ppat.1013408.ref041","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.ajog.2021.03.035","article-title":"Cord blood antibodies following maternal coronavirus disease 2019 vaccination during pregnancy","volume":"225","author":"LB Mithal","year":"2021","journal-title":"Am J Obstet Gynecol"},{"issue":"6","key":"ppat.1013408.ref042","doi-asserted-by":"crossref","first-page":"675","DOI":"10.3390\/vaccines9060675","article-title":"Evaluation of SARS-CoV-2 Spike Protein Antibody Titers in Cord Blood after COVID-19 Vaccination during Pregnancy in Polish Healthcare Workers: Preliminary Results","volume":"9","author":"W Zdanowski","year":"2021","journal-title":"Vaccines (Basel)"},{"issue":"10","key":"ppat.1013408.ref043","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1080\/21645515.2021.1947099","article-title":"Cord blood antibody following 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transfer and infant protection","volume":"16","author":"SN Langel","year":"2020","journal-title":"PLoS Pathog"},{"issue":"11","key":"ppat.1013408.ref047","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2022.40993","article-title":"Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection","volume":"5","author":"DD Flannery","year":"2022","journal-title":"JAMA Netw Open"},{"issue":"3","key":"ppat.1013408.ref048","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.cmi.2021.10.003","article-title":"Timing of SARS-CoV-2 vaccination during the third trimester of pregnancy and transplacental antibody transfer: a prospective cohort study","volume":"28","author":"A Rottenstreich","year":"2022","journal-title":"Clin Microbiol Infect"},{"issue":"13","key":"ppat.1013408.ref049","doi-asserted-by":"crossref","DOI":"10.1172\/JCI150319","article-title":"Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine","volume":"131","author":"O Beharier","year":"2021","journal-title":"J Clin Invest"},{"issue":"617","key":"ppat.1013408.ref050","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abi8631","article-title":"COVID-19 mRNA vaccines drive differential antibody Fc-functional profiles in pregnant, lactating, and nonpregnant women","volume":"13","author":"C Atyeo","year":"2021","journal-title":"Sci Transl Med"},{"issue":"2","key":"ppat.1013408.ref051","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1093\/infdis\/jiad421","article-title":"Diverging Maternal and Cord Antibody Functions From SARS-CoV-2 Infection and Vaccination in Pregnancy","volume":"229","author":"EH Adhikari","year":"2023","journal-title":"J Infect Dis"},{"issue":"1","key":"ppat.1013408.ref052","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1038\/s41467-022-31169-8","article-title":"Maternal immune response and placental antibody transfer after COVID-19 vaccination across trimester and platforms","volume":"13","author":"CG Atyeo","year":"2022","journal-title":"Nat Commun"},{"issue":"1","key":"ppat.1013408.ref053","doi-asserted-by":"crossref","first-page":"100046","DOI":"10.1016\/j.xagr.2021.100046","article-title":"Comprehensive serologic profile and specificity of maternal and neonatal cord blood SARS-CoV-2 antibodies","volume":"2","author":"RC Boelig","year":"2022","journal-title":"AJOG Glob Rep"},{"issue":"1","key":"ppat.1013408.ref054","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1002\/ijgo.14648","article-title":"Antibody response, neutralizing potency, and transplacental antibody transfer following SARS-CoV-2 infection versus mRNA-1273, BNT162b2 COVID-19 vaccination in pregnancy","volume":"162","author":"CM Dude","year":"2023","journal-title":"Int J Gynaecol Obstet"},{"issue":"1","key":"ppat.1013408.ref055","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41372-023-01843-w","article-title":"SARS-CoV-2 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