{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T08:32:23Z","timestamp":1793781143596,"version":"4.6.1"},"reference-count":48,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2012,3,28]],"date-time":"2012-03-28T00:00:00Z","timestamp":1332892800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Vet Pathol"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:p>The objective of this report was to characterize the enhanced clinical disease and lung lesions observed in pigs vaccinated with inactivated H1N2 swine \u03b4-cluster influenza A virus and challenged with pandemic 2009 A\/H1N1 human influenza virus. Eighty-four, 6-week-old, cross-bred pigs were randomly allocated into 3 groups of 28 pigs to represent vaccinated\/challenged (V\/C), non-vaccinated\/challenged (NV\/C), and non-vaccinated\/non-challenged (NV\/NC) control groups. Pigs were intratracheally inoculated with pH1N1and euthanized at 1, 2, 5, and 21 days post inoculation (dpi). Macroscopically, V\/C pigs demonstrated greater percentages of pneumonia compared to NV\/C pigs. Histologically, V\/C pigs demonstrated severe bronchointerstitial pneumonia with necrotizing bronchiolitis accompanied by interlobular and alveolar edema and hemorrhage at 1 and 2 dpi. The magnitude of peribronchiolar lymphocytic cuffing was greater in V\/C pigs by 5 dpi. Microscopic lung lesion scores were significantly higher in the V\/C pigs at 2 and 5 dpi compared to NV\/C and NV\/NC pigs. Elevated TNF-\u03b1, IL-1\u03b2, IL-6, and IL-8 were detected in bronchoalveolar lavage fluid at all time points in V\/C pigs compared to NV\/C pigs. These data suggest H1 inactivated vaccines followed by heterologous challenge resulted in potentiated clinical signs and enhanced pulmonary lesions and correlated with an elevated proinflammatory cytokine response in the lung. The lung alterations and host immune response are consistent with the vaccine-associated enhanced respiratory disease (VAERD) clinical outcome observed reproducibly in this swine model.<\/jats:p>","DOI":"10.1177\/0300985812439724","type":"journal-article","created":{"date-parts":[[2012,3,28]],"date-time":"2012-03-28T20:14:04Z","timestamp":1332965644000},"page":"900-912","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":151,"title":["Kinetics of Lung Lesion Development and Pro-Inflammatory Cytokine Response in Pigs With Vaccine-Associated Enhanced Respiratory Disease Induced by Challenge With Pandemic (2009) A\/H1N1 Influenza Virus"],"prefix":"10.1177","volume":"49","author":[{"given":"P. C.","family":"Gauger","sequence":"first","affiliation":[{"name":"Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. L.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. L.","family":"Loving","sequence":"additional","affiliation":[{"name":"Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. N.","family":"Henningson","sequence":"additional","affiliation":[{"name":"Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. M.","family":"Lager","sequence":"additional","affiliation":[{"name":"Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. H.","family":"Janke","sequence":"additional","affiliation":[{"name":"Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"M. E.","family":"Kehrli","sequence":"additional","affiliation":[{"name":"Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA, Agricultural Research Service, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. A.","family":"Roth","sequence":"additional","affiliation":[{"name":"Veterinary Microbiology and Preventive Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2012,3,28]]},"reference":[{"key":"bibr1-0300985812439724","author":"Beaudoin A","journal-title":"Zoonoses Public Health"},{"key":"bibr2-0300985812439724","first-page":"312","volume":"60","author":"Bikour MH","year":"1996","journal-title":"Can J Vet Res"},{"key":"bibr3-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1702(02)00053-9"},{"key":"bibr4-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1894"},{"key":"bibr5-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1967.03130250057008"},{"key":"bibr6-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176225"},{"key":"bibr7-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2011.05.038"},{"key":"bibr8-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.01.082"},{"key":"bibr9-0300985812439724","doi-asserted-by":"crossref","first-page":"1926","DOI":"10.2460\/ajvr.1985.46.09.1926","volume":"46","author":"Haesebrouck F","year":"1985","journal-title":"Am J Vet Res"},{"key":"bibr10-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1135(86)90026-X"},{"key":"bibr11-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1177\/030098589503200606"},{"key":"bibr12-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-83-8-1851"},{"key":"bibr13-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.9.7367-7373.1998"},{"key":"bibr14-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a120955"},{"key":"bibr15-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2006.02.008"},{"key":"bibr16-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.09.130"},{"key":"bibr17-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/170.4.802"},{"key":"bibr18-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.027557-0"},{"key":"bibr19-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.80.10.5092-5096.2006"},{"key":"bibr20-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1111\/j.1863-2378.2008.01217.x"},{"key":"bibr21-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.2.1491-1496.1998"},{"key":"bibr22-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2262"},{"key":"bibr23-0300985812439724","first-page":"1271","volume":"26","author":"Nayak DP","year":"1965","journal-title":"Am J Vet Res"},{"key":"bibr24-0300985812439724","doi-asserted-by":"publisher","DOI":"10.3201\/eid1207.060268"},{"key":"bibr25-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1354\/vp.40-5-521"},{"key":"bibr26-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1038\/nm918"},{"key":"bibr27-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020781"},{"key":"bibr28-0300985812439724","first-page":"493","volume":"1938","author":"Reed LJ","year":"1938","journal-title":"Am J Infect Control"},{"key":"bibr29-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.41.7.3198-3205.2003"},{"key":"bibr30-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00787-06"},{"key":"bibr31-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000258"},{"key":"bibr32-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.02366-07"},{"key":"bibr33-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.44.2.303-330.1980"},{"key":"bibr34-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1086\/517398"},{"key":"bibr35-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1089\/088282402320914520"},{"key":"bibr36-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2004.02.023"},{"key":"bibr37-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-2659.2009.00121.x"},{"key":"bibr38-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2007.07.011"},{"key":"bibr39-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2006.07.017"},{"key":"bibr40-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1007\/s11262-009-0386-6"},{"key":"bibr41-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3527(08)00403-X"},{"key":"bibr42-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2009.01.003"},{"key":"bibr43-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1177\/104063879700900214"},{"key":"bibr44-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.18.8243-8251.2000"},{"key":"bibr45-0300985812439724","unstructured":"WHO. WHO Manual on Animal Influenza Diagnosis and Surveillance. 2nd ed. http:\/\/www.wpro.who.int\/NR\/rdonlyres\/EFD2B9A7-2265-4AD0-BC98-97937B4FA83C\/0\/manualonanimalaidiagnosisandsurveillance.pdf.Published2002. Accessed June 14, 2010."},{"key":"bibr46-0300985812439724","first-page":"541","volume":"122","author":"Winkler GC","year":"1986","journal-title":"Am J Pathol"},{"key":"bibr47-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.10.8851-8856.1999"},{"key":"bibr48-0300985812439724","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(00)00165-6"}],"container-title":["Veterinary Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0300985812439724","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0300985812439724","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0300985812439724","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T18:52:00Z","timestamp":1777661520000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0300985812439724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,28]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2012,11]]}},"alternative-id":["10.1177\/0300985812439724"],"URL":"https:\/\/doi.org\/10.1177\/0300985812439724","relation":{},"ISSN":["0300-9858","1544-2217"],"issn-type":[{"value":"0300-9858","type":"print"},{"value":"1544-2217","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,28]]}}}