{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T14:22:53Z","timestamp":1762957373857,"version":"3.41.2"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common throughout life. Maternal vaccination has emerged as a promising strategy, delivering elevated antibody levels to newborns for immediate protection. However, limited research has explored the protective efficacy of maternal antibodies (matAbs) against secondary RSV infections in offspring. To address this gap, we employed a mouse model of maternal RSV vaccination and secondary infection of offspring to evaluate lung pathology following RSV reinfection in mice with varying levels of maternal antibody (matAb). Additionally, we aimed to investigate the potential causes of exacerbated lung inflammation in offspring with high matAb levels following secondary RSV exposure. Our findings revealed that offspring with elevated levels of maternal pre-F antibody demonstrated effective protection against lung pathology following the initial RSV infection. However, this protection was compromised upon reinfection, manifesting as heightened weight loss, exacerbated lung pathology, increased expression of RSV-A N genes, eosinophilia, enhanced IL-5, IL-13, MUC5AC, and eosinophils Major Basic Protein (MBP) production in lung tissue compared to offspring lacking matAbs. Importantly, these unexpected outcomes were not attributed to antibody-dependent enhancement (ADE) resulting from declining matAb levels over time. Notably, our findings showed a decline in secretory IgA (sIgA), mucosal IgA, and mucosal IgG levels in offspring with high matAb levels post-primary RSV challenge. We propose that this decline may be a critical factor contributing to the ineffective protection observed during secondary RSV exposure. Overall, these findings offer valuable insights into maternal vaccination against RSV, contributing to a comprehensive understanding and mitigation of potential risks associated with maternal RSV vaccination.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1377374","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T04:51:20Z","timestamp":1714452680000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Exacerbated lung inflammation in offspring with high maternal antibody levels following secondary RSV exposure"],"prefix":"10.3389","volume":"15","author":[{"given":"Jinhua","family":"Ma","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuanglian","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenghao","family":"Mei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huaqin","family":"Bu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenxing","family":"Jia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohu","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoli","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhou","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiyin","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30938-8","article-title":"Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: A systematic review and modelling study","volume":"390","author":"Shi","year":"2017","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2019.1596710","article-title":"Rsv recombinant candidate vaccine G1f\/M2 with cpg as an adjuvant prevents vaccine-associated lung inflammation, which may be associated with the appropriate types of immune memory in spleens and lungs","volume":"15","author":"Li","year":"2019","journal-title":"Hum Vaccin Immunother"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-38919-1_8","article-title":"The adaptive immune response to respiratory syncytial virus","volume":"372","author":"Varga","year":"2013","journal-title":"Curr Top Microbiol Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1093\/aje\/kws257","article-title":"The natural history of respiratory syncytial virus in a birth cohort: the influence of age and previous infection on reinfection and disease","volume":"176","author":"Ohuma","year":"2012","journal-title":"Am J Epidemiol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1086\/524019","article-title":"Respiratory syncytial virus infection and disease in infants and young children observed from birth in Kilifi district, Kenya","volume":"46","author":"Nokes","year":"2008","journal-title":"Clin Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1017\/S0950268815003143","article-title":"Prospective clinical and serological follow-up in early childhood reveals a high rate of subclinical rsv infection and a relatively high reinfection rate within the first 3 years of life","volume":"144","author":"Kutsaya","year":"2016","journal-title":"Epidemiol Infect"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2013.05.003","article-title":"The path to an rsv vaccine","volume":"3","author":"Shaw","year":"2013","journal-title":"Curr Opin Virol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1093\/infdis\/jiy477","article-title":"Breast milk prefusion F immunoglobulin G as a correlate of protection against respiratory syncytial virus acute respiratory illness","volume":"219","author":"Mazur","year":"2019","journal-title":"J Infect Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiz390","article-title":"Safety and immunogenicity of a respiratory syncytial virus fusion (F) protein nanoparticle vaccine in healthy third-trimester pregnant women and their infants","volume":"220","author":"Munoz","year":"2019","journal-title":"J Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908380","article-title":"Respiratory syncytial virus vaccination during pregnancy and effects in infants","volume":"383","author":"Madhi","year":"2020","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1177\/2515135520981516","article-title":"Strategies for active and passive pediatric rsv immunization","volume":"9","author":"Eichinger","year":"2021","journal-title":"Ther Adv Vaccines Immunother"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2019.11.003","article-title":"Maternal immunization with rsv fusion glycoprotein vaccine and substantial protection of neonatal baboons against respiratory syncytial virus pulmonary challenge","volume":"38","author":"Welliver","year":"2020","journal-title":"Vaccine"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020943","article-title":"Age at first viral infection determines the pattern of T cell-mediated disease during reinfection in adulthood","volume":"196","author":"Culley","year":"2002","journal-title":"J Exp Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-7-107","article-title":"Exposure of neonates to respiratory syncytial virus is critical in determining subsequent airway response in adults","volume":"7","author":"You","year":"2006","journal-title":"Respir Res"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890260207","article-title":"Primary respiratory syncytial virus infection in mice","volume":"26","author":"Graham","year":"1988","journal-title":"J Med Virol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006640","article-title":"Early il-6 signalling promotes il-27 dependent maturation of regulatory T cells in the lungs and resolution of viral immunopathology","volume":"13","author":"Pyle","year":"2017","journal-title":"PloS Pathog"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-010-9503-5","article-title":"The antiasthma effect of neonatal bcg vaccination does not depend on the th17\/th1 but il-17\/ifn-\u0393 Balance in a balb\/C mouse asthma model","volume":"31","author":"Deng","year":"2011","journal-title":"J Clin Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-015-0176-8","article-title":"Mmp-12-mediated by sarm-trif signaling pathway contributes to ifn-\u0393-independent airway inflammation and ahr post rsv infection in nude mice","volume":"16","author":"Long","year":"2015","journal-title":"Respir Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1769","article-title":"Il-13 and ifn-gamma: interactions in lung inflammation","volume":"167","author":"Ford","year":"2001","journal-title":"J Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1084\/jem.20040616","article-title":"Spred-1 negatively regulates allergen-induced airway eosinophilia and hyperresponsiveness","volume":"201","author":"Inoue","year":"2005","journal-title":"J Exp Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2000.105712","article-title":"Mechanisms of eosinophil-associated inflammation","volume":"105","author":"Gleich","year":"2000","journal-title":"J Allergy Clin Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/824362","article-title":"Distribution of major basic protein on human airway following in vitro eosinophil incubation","volume":"2010","author":"Xue","year":"2010","journal-title":"Mediators Inflammation"},{"key":"B23","doi-asserted-by":"publisher","first-page":"994","DOI":"10.3109\/02770903.2011.623335","article-title":"Eosinophil degranulation is more important than eosinophilia in identifying asthma in chronic cough","volume":"48","author":"Kim","year":"2011","journal-title":"J Asthma"},{"key":"B24","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1620\/tjem.233.49","article-title":"Expression levels of eosinophil granule protein mrnas in induced sputum reflect airway hyperresponsiveness and airflow limitation","volume":"233","author":"Jung","year":"2014","journal-title":"Tohoku J Exp Med"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.3.1876","article-title":"The enhancement or prevention of airway hyperresponsiveness during reinfection with respiratory syncytial virus is critically dependent on the age at first infection and il-13 production","volume":"175","author":"Dakhama","year":"2005","journal-title":"J Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201412-2256OC","article-title":"Impaired antibody-mediated protection and defective iga B-cell memory in experimental infection of adults with respiratory syncytial virus","volume":"191","author":"Habibi","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1038\/s41467-019-09085-1","article-title":"Systematic comparison of respiratory syncytial virus-induced memory B cell responses in two anatomical compartments","volume":"10","author":"Shehata","year":"2019","journal-title":"Nat Commun"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00590-15","article-title":"Mucosal igg levels correlate better with respiratory syncytial virus load and inflammation than plasma igg levels","volume":"23","author":"Vissers","year":"2015","journal-title":"Clin Vaccine Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.15475.1","article-title":"Maternal immunisation: what have been the gains? Where are the gaps? What does the future hold","volume":"7","author":"Giles","year":"2018","journal-title":"F1000Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"309ra162","DOI":"10.1126\/scitranslmed.aac4241","article-title":"Prefusion F-specific antibodies determine the magnitude of rsv neutralizing activity in human sera","volume":"7","author":"Ngwuta","year":"2015","journal-title":"Sci Transl Med"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix489","article-title":"and disease severity in infants and young children with acute respiratory syncytial virus infection","volume":"216","author":"Capella","year":"2017","journal-title":"J Infect Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2017.03.012","article-title":"Vaccine development for respiratory syncytial virus","volume":"23","author":"Graham","year":"2017","journal-title":"Curr Opin Virol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20142284","article-title":"Distinct germinal center selection at local sites shapes memory B cell response to viral escape","volume":"212","author":"Adachi","year":"2015","journal-title":"J Exp Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abb6808","article-title":"T resident helper cells promote humoral responses in the lung","volume":"6","author":"Swarnalekha","year":"2021","journal-title":"Sci Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2011.39","article-title":"Structure and function relationships in iga","volume":"4","author":"Woof","year":"2011","journal-title":"Mucosal Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.jaci.2008.10.043","article-title":"Respiratory syncytial virus neutralizing antibodies in cord blood, respiratory syncytial virus hospitalization, and recurrent wheeze","volume":"123","author":"Stensballe","year":"2009","journal-title":"J Allergy Clin Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1377374\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T04:51:26Z","timestamp":1714452686000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1377374\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,30]]},"references-count":36,"alternative-id":["10.3389\/fimmu.2024.1377374"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1377374","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2024,4,30]]},"article-number":"1377374"}}