{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T19:05:58Z","timestamp":1778526358432,"version":"3.51.4"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants. Despite over 50 years of research, to date no safe and efficacious RSV vaccine has been licensed. Many experimental vaccination strategies failed to induce balanced T-helper (Th) responses and were associated with adverse effects such as hypersensitivity and immunopathology upon challenge. In this study, we explored the well-established recombinant vaccinia virus (rVV) RSV-F\/RSV-G vaccination-challenge mouse model to study phenotypically distinct vaccine-mediated host immune responses at the proteome level. In this model, rVV-G priming and not rVV-F priming results in the induction of Th2 skewed host responses upon RSV challenge. Mass spectrometry-based spectral count comparisons enabled us to identify seven host proteins for which expression in lung tissue is associated with an aberrant Th2 skewed response characterized by the influx of eosinophils and neutrophils. These proteins are involved in processes related to the direct influx of eosinophils (eosinophil peroxidase [Epx]) and to chemotaxis and extravasation processes (Chil3 [chitinase-like-protein 3]) as well as to eosinophil and neutrophil homing signals to the lung (Itgam). In addition, the increased levels of Arg1 and Chil3 proteins point to a functional and regulatory role for alternatively activated macrophages and type 2 innate lymphoid cells in Th2 cytokine-driven RSV vaccine-mediated enhanced disease.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>RSV alone is responsible for 80% of acute bronchiolitis cases in infants worldwide and causes substantial mortality in developing countries. Clinical trials performed with formalin-inactivated RSV vaccine preparations in the 1960s failed to induce protection upon natural RSV infection and even predisposed patients for enhanced disease. Despite the clinical need, to date no safe and efficacious RSV vaccine has been licensed. Since RSV vaccines have a tendency to prime for unbalanced responses associated with an exuberant influx of inflammatory cells and enhanced disease, detailed characterization of primed host responses has become a crucial element in RSV vaccine research. We investigated the lung proteome of mice challenged with RSV upon priming with vaccine preparations known to induce phenotypically distinct host responses. Seven host proteins whose expression levels are associated with vaccine-mediated enhanced disease have been identified. The identified protein biomarkers support the development as well as detailed evaluation of next-generation RSV vaccines.<\/jats:p>","DOI":"10.1128\/jvi.03630-14","type":"journal-article","created":{"date-parts":[[2015,2,19]],"date-time":"2015-02-19T06:34:38Z","timestamp":1424327678000},"page":"5022-5031","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Host Proteome Correlates of Vaccine-Mediated Enhanced Disease in a Mouse Model of Respiratory Syncytial Virus Infection"],"prefix":"10.1128","volume":"89","author":[{"given":"Angela","family":"van Diepen","sequence":"first","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Kim","family":"Brand","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon","family":"de Waal","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands"},{"name":"Viroclinics Biosciences B.V., Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maarten","family":"Bijl","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor L.","family":"Jong","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands"},{"name":"Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thijs","family":"Kuiken","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geert","family":"van Amerongen","sequence":"additional","affiliation":[{"name":"Viroclinics Biosciences B.V., Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henk-Jan","family":"van den Ham","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marinus J.","family":"Eijkemans","sequence":"additional","affiliation":[{"name":"Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert D. M. E.","family":"Osterhaus","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter W. M.","family":"Hermans","sequence":"additional","affiliation":[{"name":"Laboratory of Pediatric Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arno C.","family":"Andeweg","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39374.600081.AD"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)80040-3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60206-1"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a120957"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a120956"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a120954"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a120955"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(01)00301-2"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.08.014"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2013.04.011"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00302-10"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(00)00213-9"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.19.7462"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/4.4.493"},{"key":"e_1_3_2_16_2","first-page":"493","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed LJ","year":"1938","unstructured":"Reed LJ, Muench H. 1938. A simple method of estimating fifty percent endpoints. Am J Hyg (Lond) 27:493\u2013497.","journal-title":"Am J Hyg (Lond)"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.60.2.607-613.1986"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2004.03.004"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh036"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M800203-MCP200"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511814365"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/biomet\/10.1.36"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2010-11-10-r106"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.5613"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-189886"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.2741\/2767"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2007.10.022"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.4161\/hv.6.6.11562"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-82-12-2881"},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.4049\/jimmunol.151.4.2032","article-title":"Priming immunization determines T helper cytokine mRNA expression patterns in lungs of mice challenged with respiratory syncytial virus","volume":"151","author":"Graham BS","year":"1993","unstructured":"Graham BS, Henderson GS, Tang Y, Xiaotao L, Neuzil KM, Colley DG. 1993. Priming immunization determines T helper cytokine mRNA expression patterns in lungs of mice challenged with respiratory syncytial virus. J Immunol 151:2032\u20132040.","journal-title":"J Immunol"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.10.6692"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.22.11561-11569.2002"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.2.1279"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010417200"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2005-0134OC"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20110101"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2008.82"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/137.6.1602S"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0710409"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-06-032599"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.021908.132532"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0213084"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606489200"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2002.121555"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0707413104"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0366-6999.2010.12.022"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082367"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013823"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24237"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.03630-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.03630-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,6]],"date-time":"2023-08-06T12:44:31Z","timestamp":1691325871000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.03630-14"}},"subtitle":[],"editor":[{"given":"D. S.","family":"Lyles","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2015,5]]},"references-count":48,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1128\/JVI.03630-14"],"URL":"https:\/\/doi.org\/10.1128\/jvi.03630-14","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5]]},"assertion":[{"value":"2014-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}