{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:09:24Z","timestamp":1792976964062,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["VIR\/78\/2013\/ECD\u2010I"],"award-info":[{"award-number":["VIR\/78\/2013\/ECD\u2010I"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100022833","name":"Rajiv Gandhi Centre for Biotechnology, Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR30213\/MED\/15\/191\/2018"],"award-info":[{"award-number":["BT\/PR30213\/MED\/15\/191\/2018"]}],"id":[{"id":"10.13039\/100022833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,12]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background and Aim<\/jats:title>\n High levels of HBV DNA and HBsAg titres increase the risk of mother\u2010to\u2010child transmission. Development of adaptive immunity post HBV vaccination in neonates born to HBsAg\u2010positive mothers may be determined by maternal HBsAg titres. We analysed pre\u2010 and post\u2010HBV vaccination immune status in neonates.<\/jats:p>\n <\/jats:sec>\n \n Method<\/jats:title>\n \n PBMCs were collected before and after vaccination for single cell multi\u2010omics sequencing for infants born to mothers with low (Gr.1, sAg\n Lo<\/jats:sup>\n 1.65\u2009\u00d7\u200910\n 2<\/jats:sup>\n \u2009IU\/mL) and high (Gr.2, sAg\n Hi<\/jats:sup>\n 1.4\u2009\u00d7\u200910\n 4<\/jats:sup>\n IU\/mL) HBsAg titres. Integrative analysis of whole transcriptome and surface marker expression was done using the Seurat R package. Functional validation of single\u2010cell data was performed through immunophenotyping in both groups.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n scRNAseq revealed that, at pre\u2010HBV vaccine, CD8\n +<\/jats:sup>\n T cells of neonates born to mothers with HBsAg\n Hi<\/jats:sup>\n levels showed increased expression (\n p<\/jats:italic>\n \u2009<\u20090.05) of TOX, CTLA4, PD1, LAG3, CD38 and CREM exhaustion markers and decreased expression of ATP1B3, MREG and TGF\u03b21 compared to sAg\n Lo<\/jats:sup>\n . Monocytes and NK cells had elevated CXCR3, TNFSF9, HIVEP3, WDPCP, ATP6V1G2, IL\u20106, GMCSF and GCSF (\n p<\/jats:italic>\n \u2009<\u20090.0001) driving the inflammation and mitochondrial biogenesis through MAP\/ERK kinase in sAg\n Hi<\/jats:sup>\n compared to sAg\n Lo<\/jats:sup>\n . Post\u2010vaccination, despite anti\u2010HBs titre \u2265\u200910\u2009IU\/mL, sAg\n Hi<\/jats:sup>\n , neonates showed persistently high TOX, CTLA4, PD1 and CREM in CD8\n +<\/jats:sup>\n T cells (\n p<\/jats:italic>\n \u2009<\u20090.0001). Functional validations by immune phenotyping also showed higher expression of LAG3, PD1, TIGIT and BTLA (\n p<\/jats:italic>\n \u2009<\u20090.05) on CD8\n +<\/jats:sup>\n T cells pre\u2010 and post\u2010vaccination in sAg\n Hi<\/jats:sup>\n compared to sAg\n Lo<\/jats:sup>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n HBV exposure compromises adaptive immunity at birth; despite post\u2010vaccination anti\u2010HBs titres generation, there was a sustained pro\u2010inflammatory state by the innate immune activation via metabolic alterations that persisted in neonates born to sAg\n Hi<\/jats:sup>\n mothers.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/liv.70405","type":"journal-article","created":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T07:32:37Z","timestamp":1762587157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["scRNA<\/scp>\n \u2010Seq Reveals Sustained Pro\u2010Inflammation by Innate Immune Activation in In Utero\n HBV\u2010<\/scp>\n Exposed Neonates of High\n HBsAg<\/scp>\n Mothers"],"prefix":"10.1111","volume":"45","author":[{"given":"Prabhjyoti","family":"Pahwa","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Medicine Institute of Liver and Biliary Sciences New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravinder","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine Institute of Liver and Biliary Sciences New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Partha","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priyanka","family":"Mehta","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish Kumar","family":"Vyas","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine Institute of Liver and Biliary Sciences New Delhi India"},{"name":"Amrita Research Center, Delhi NCR, Amrita Vishwa Vidyapeetham Faridabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharda","family":"Patra","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology Lady Harding Medical College New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shakun","family":"Tyagi","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics Lok Nayak Jai Prakash Hospital New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4404-8327","authenticated-orcid":false,"given":"Rajesh","family":"Pandey","sequence":"additional","affiliation":[{"name":"Academy of Scientific and Innovative Research (AcSIR) Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0544-5610","authenticated-orcid":false,"given":"Shiv Kumar","family":"Sarin","sequence":"additional","affiliation":[{"name":"Department of Hepatology Institute of Liver and Biliary Sciences New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6109-0033","authenticated-orcid":false,"given":"Nirupama","family":"Trehanpati","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Medicine Institute of Liver and Biliary Sciences New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,7]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Centers for Disease Control and Prevention \u201cHepatitis B. 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