{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T11:26:10Z","timestamp":1787570770742,"version":"build-2736575974"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":70,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Maternal immunisation allows the transfer of protective antibodies to the offspring, reducing the risk of severe infection during early life. While vaccination during pregnancy is clinically recommended, its long-term impact on neurodevelopment remains under investigation. Autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by social and behavioural alterations. Here, we evaluated whether prenatal exposure to the COVID-19 mRNA BNT162b2 vaccine or influenza vaccine affects general and autism-related behavioural outcomes in juvenile (4 weeks) and adult (8 weeks) mouse offspring. We also assessed maternal and fetal immune responses by measuring cytokines, soluble P2X7 receptor, BDNF, CRP, and lipid peroxidation in maternal plasma and fetal brain tissue. Prenatal COVID-19 vaccination elicited a moderate maternal cytokine response (increased IL-6 and KC) without overt fetal brain inflammation. Mild, age- and sex-dependent behavioural changes were observed, including anxiety-related parameters in the elevated plus maze and altered locomotion in the open field at 4\u20138 weeks, however, no consistent or robust ASD-like behavioural phenotype emerged across ages. Fetal P2X7 receptor levels were elevated, while fetal CRP, BDNF, and TBARS remained unchanged. In adult offspring, BDNF was selectively reduced in the prefrontal cortex, whereas hippocampal BDNF and P2X7 receptor levels in both regions were unaffected. Although embryonic P2X7 receptor levels were transiently elevated following COVID-19 vaccination, these changes were not accompanied by fetal inflammation or persistent adult purinergic alterations. Prenatal influenza vaccination induced mild, age-dependent behavioural alterations, such as increased circling in juveniles and reduced sociability in females, without detectable maternal or fetal inflammatory responses or changes in fetal neurotrophic markers. In contrast, maternal poly(I:C) administration provoked robust systemic inflammation and pronounced fetal brain effects, including elevated cytokines, CRP, P2X7 receptor, and region-specific microglial density, accompanied by persistent reductions in adult BDNF expression. Overall, within the limits of this experimental design, prenatal COVID-19 vaccination did not produce long-lasting ASD-like phenotypes or widespread neurodevelopmental alterations, while influenza vaccination had limited and transient effects. These findings are consistent with the absence of widespread or persistent neurodevelopmental disruption in this experimental model, although further studies\u2014including multiple doses, gestational timepoints, and cellular-level analyses\u2014are warranted to fully elucidate mechanisms and long-term outcomes.<\/jats:p>","DOI":"10.1038\/s41398-026-04147-7","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T13:05:19Z","timestamp":1781528719000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring offspring behaviour after prenatal COVID-19 vaccination in mice"],"prefix":"10.1038","volume":"16","author":[{"given":"Lilla","family":"Otrokocsi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fruzsina","family":"Ma\u00e1cz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e1l","family":"Tod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2965-3044","authenticated-orcid":false,"given":"Fl\u00f3ra","family":"G\u00f6l\u00f6ncs\u00e9r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Be\u00e1ta","family":"Sperl\u00e1gh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"4147_CR1","doi-asserted-by":"publisher","unstructured":"Gray KJ, Bordt EA, Atyeo C, Deriso E, Akinwunmi B, Young N, et al. Coronavirus disease 2019 vaccine response inpregnant and lactating women: a cohort study. Am J Obstet Gynecol. 2021;225(3):303 e1- e17. Epub 2021\/03\/30. https:\/\/doi.org\/10.1016\/j.ajog.2021.03.023.","DOI":"10.1016\/j.ajog.2021.03.023"},{"issue":"23","key":"4147_CR2","doi-asserted-by":"publisher","first-page":"2370","DOI":"10.1001\/jama.2021.7563","volume":"325","author":"AY Collier","year":"2021","unstructured":"Collier AY, McMahan K, Yu J, Tostanoski LH, Aguayo R, Ansel J, et al. Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. JAMA. 2021;325(23):2370\u201380. https:\/\/doi.org\/10.1001\/jama.2021.7563. Epub 2021\/05\/14PubMed PMID: 33983379; PubMed Central PMCID: PMCPMC8120446 and owns shares of SeromYx Systems Inc. Dr Linde reported that she is an employee of SeromYx Systems Inc. Dr Alter reported cofounding and serving as a consultant to, and having a patent pending through SeromYx Systems Inc. Dr Barouch reported receiving grants from National Institutes of Health (NIH), the Henry M. Jackson Foundation of the Walter Reed Army Institute of Research, the Bill and Melinda Gates Foundation, the Defense Advanced Research Projects Agency, Gilead, Intima, Alkermes, CureVac, South Africa Medical Research Council, amfAR, Ragon Institute, MassCPR, Sanofi, Legend, and Zentalis; receiving personal fees from SQZ Biotech; and having a patent for COVID-19 vaccines licensed to Janssen with no premarket royalties or payments of any kind. No other disclosures were reported.","journal-title":"JAMA"},{"issue":"24","key":"4147_CR3","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.1056\/NEJMoa2104983","volume":"384","author":"TT Shimabukuro","year":"2021","unstructured":"Shimabukuro TT, Kim SY, Myers TR, Moro PL, Oduyebo T, Panagiotakopoulos L, et al. Preliminary findings of mRNA Covid-19 vaccine safety in pregnant persons. N Engl J Med. 2021;384(24):2273\u201382. https:\/\/doi.org\/10.1056\/NEJMoa2104983.","journal-title":"N Engl J Med."},{"issue":"4","key":"4147_CR4","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13934","volume":"92","author":"C Zhong","year":"2024","unstructured":"Zhong C, Cohen K, Lin X, Schiller E, Sharma S, Hanna N. COVID-19 vaccine mRNA biodistribution: maternal and fetal exposure risks. Am J Reprod Immunol. 2024;92(4):e13934. https:\/\/doi.org\/10.1111\/aji.13934.","journal-title":"Am J Reprod Immunol"},{"key":"4147_CR5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2022.136974","volume":"793","author":"ML Dutra","year":"2023","unstructured":"Dutra ML, Dias P, Freiberger V, Ventura L, Comim CM, Martins DF, et al. Maternal immune activation induces autism-like behavior and reduces brain-derived neurotrophic factor levels in the hippocampus and offspring cortex of C57BL\/6 mice. Neurosci Lett. 2023;793:136974. https:\/\/doi.org\/10.1016\/j.neulet.2022.136974.","journal-title":"Neurosci Lett"},{"key":"4147_CR6","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1016\/j.neubiorev.2020.04.012","volume":"113","author":"FL Haddad","year":"2020","unstructured":"Haddad FL, Patel SV, Schmid S. Maternal immune activation by poly I:C as a preclinical Model for neurodevelopmental disorders: a focus on autism and schizophrenia. Neurosci Biobehav Rev. 2020;113:546\u201367. https:\/\/doi.org\/10.1016\/j.neubiorev.2020.04.012.","journal-title":"Neurosci Biobehav Rev"},{"key":"4147_CR7","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.neuroscience.2020.05.009","volume":"445","author":"D Vigli","year":"2020","unstructured":"Vigli D, Palombelli G, Fanelli S, Calamandrei G, Canese R, Mosca L, et al. Maternal immune activation in mice only partially recapitulates the autism spectrum disorders symptomatology. Neuroscience. 2020;445:109\u201319. https:\/\/doi.org\/10.1016\/j.neuroscience.2020.05.009.","journal-title":"Neuroscience"},{"key":"4147_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2024.105844","volume":"164","author":"S Sal-Sarria","year":"2024","unstructured":"Sal-Sarria S, Conejo NM, Gonzalez-Pardo H. Maternal immune activation and its multifaceted effects on learning and memory in rodent offspring: A systematic review. Neurosci Biobehav Rev. 2024;164:105844. https:\/\/doi.org\/10.1016\/j.neubiorev.2024.105844.","journal-title":"Neurosci Biobehav Rev"},{"issue":"1","key":"4147_CR9","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03106-7","volume":"21","author":"HC Osman","year":"2024","unstructured":"Osman HC, Moreno R, Rose D, Rowland ME, Ciernia AV, Ashwood P. Impact of maternal immune activation and sex on placental and fetal brain cytokine and gene expression profiles in a preclinical model of neurodevelopmental disorders. J Neuroinflammation. 2024;21(1):118. https:\/\/doi.org\/10.1186\/s12974-024-03106-7.","journal-title":"J Neuroinflammation"},{"key":"4147_CR10","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1016\/j.bbi.2022.01.015","volume":"101","author":"D Szabo","year":"2022","unstructured":"Szabo D, Tod P, Goloncser F, Roman V, Lendvai B, Otrokocsi L, et al. Maternal P2X7 receptor inhibition prevents autism-like phenotype in male mouse offspring through the NLRP3-IL-1beta pathway. Brain Behav Immun. 2022;101:318\u201332. https:\/\/doi.org\/10.1016\/j.bbi.2022.01.015.","journal-title":"Brain Behav Immun"},{"issue":"13","key":"4147_CR11","doi-asserted-by":"publisher","first-page":"2542","DOI":"10.1523\/JNEUROSCI.1895-18.2019","volume":"39","author":"G Horvath","year":"2019","unstructured":"Horvath G, Otrokocsi L, Beko K, Baranyi M, Kittel A, Fritz-Ruenes PA, et al. P2X7 Receptors Drive Poly(I:C) induced autism-like behavior in mice. 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Prenatal exposure to COVID-19 mRNA vaccine BNT162b2 induces autism-like behaviors in male neonatal rats: insights into WNT and BDNF signaling perturbations. Neurochem Res. 2024;49(4):1034\u201348. https:\/\/doi.org\/10.1007\/s11064-023-04089-2.","journal-title":"Neurochem Res."},{"issue":"3","key":"4147_CR16","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/S2352-4642(25)00008-2","volume":"9","author":"I Hardie","year":"2025","unstructured":"Hardie I, Marryat L, Murray A, King J, Okelo K, Boardman JP, et al. Early childhood developmental concerns following SARS-CoV-2 infection and COVID-19 vaccination during pregnancy: a Scottish population-level retrospective cohort study. 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Dr Perlis reported receiving consulting fees from Burrage Capital, Genomind, RID Ventures, Belle Artificial Intelligence, and Takeda; he reported receiving equity in Psy Therapeutics, Belle Artificial Intelligence, and Circular Genomics; Dr Perlis also reported receiving personal fees from Genomind Scientific Advisory Board and personal fees from Vault Health Scientific Advisory Board outside the submitted work. No other disclosures were reported.","journal-title":"JAMA Netw Open"},{"issue":"3","key":"4147_CR18","doi-asserted-by":"publisher","first-page":"e234415","DOI":"10.1001\/jamanetworkopen.2023.4415","volume":"6","author":"AG Edlow","year":"2023","unstructured":"Edlow AG, Castro VM, Shook LL, Haneuse S, Kaimal AJ, Perlis RH. Sex-specific neurodevelopmental outcomes among offspring of mothers with SARS-CoV-2 infection during pregnancy. JAMA Netw Open. 2023;6(3):e234415 https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.4415. PubMed PMID: 36951861; PubMed Central PMCID: PMCPMC10037162 the National Institutes of Health outside the submitted work, receiving grant funding from Simons Foundation Autism Research Initiative (SFARI) during the conduct of the study, and consulting for Mirvie Inc outside the submitted work. Dr Shook reported receiving grant funding from the National Institute of Childhood Health and Development (NICHD) during the conduct of the study. Dr Perlis reported receiving personal fees from Genomind, Burrage Capital, Psy Therapeutics Inc, Circular Genomics Inc, and Vault Health outside the submitted work. No other disclosures were reported.","journal-title":"JAMA Netw Open"},{"issue":"5","key":"4147_CR19","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1038\/s41380-024-02808-x","volume":"30","author":"RA Hill","year":"2025","unstructured":"Hill RA, Gibbons A, Suwakulsiri W, Taseska A, Darke H, Malhotra A, et al. Investigating the impact of severe maternal SARS-CoV-2 infection on infant DNA methylation and neurodevelopment. Mol Psychiatry. 2025;30(5):1976\u201384. https:\/\/doi.org\/10.1038\/s41380-024-02808-x.","journal-title":"Mol Psychiatry"},{"key":"4147_CR20","doi-asserted-by":"publisher","unstructured":"Tang Q, Wang X, Yang F, Liang L, Li Y, Liu W, et al. Pathophysiological associations between maternal immune activation and neurodevelopmental disorders in offspring: a comprehensive review. Front endocrinol (Lausanne). 2025;16. https:\/\/doi.org\/10.3389\/fendo.2025.1681190.","DOI":"10.3389\/fendo.2025.1681190"},{"key":"4147_CR21","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.reprotox.2021.05.007","volume":"103","author":"CJ Bowman","year":"2021","unstructured":"Bowman CJ, Bouressam M, Campion SN, Cappon GD, Catlin NR, Cutler MW, et al. 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This data-only study was approved by the KPNC Institutional Review Board (Protocol #1674365), which waived the requirement for informed consent from participants.","journal-title":"Transl Psychiatry"},{"issue":"2","key":"4147_CR31","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1093\/ijnp\/pyab087","volume":"25","author":"Y Su","year":"2022","unstructured":"Su Y, Lian J, Hodgson J, Zhang W, Deng C. Prenatal Poly I:C challenge affects behaviors and neurotransmission via elevated neuroinflammation responses in female juvenile rats. Int J Neuropsychopharmacol. 2022;25(2):160\u201371. https:\/\/doi.org\/10.1093\/ijnp\/pyab087.","journal-title":"Int J Neuropsychopharmacol."},{"key":"4147_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2023.137467","volume":"814","author":"S Fujii","year":"2023","unstructured":"Fujii S, Murata Y, Imamura Y, Nakachi Y, Bundo M, Kubota-Sakashita M, et al. Sex-dependent behavioral alterations in a poly(I:C)-induced maternal immune activation mouse model without segment filamentous bacteria. Neurosci Lett. 2023;814:137467. https:\/\/doi.org\/10.1016\/j.neulet.2023.137467.","journal-title":"Neurosci Lett"},{"issue":"1","key":"4147_CR33","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-28919-z","volume":"13","author":"K Gzielo","year":"2023","unstructured":"Gzielo K, Piotrowska D, Litwa E, Popik P, Nikiforuk A. Maternal immune activation affects socio-communicative behavior in adult rats. Sci Rep. 2023;13(1):1918. https:\/\/doi.org\/10.1038\/s41598-023-28919-z.","journal-title":"Sci Rep."},{"issue":"5","key":"4147_CR34","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.91","volume":"6","author":"SE Gilman","year":"2016","unstructured":"Gilman SE, Cherkerzian S, Buka SL, Hahn J, Hornig M, Goldstein JM. Prenatal immune programming of the sex-dependent risk for major depression. 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