Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus.
<h4>Background</h4>Severe acute respiratory syndrome (SARS) emerged in China in 2002 and spread to other countries before brought under control. Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated. Evaluations of an inac...
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0035421&type=printable |
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| author | Chien-Te Tseng Elena Sbrana Naoko Iwata-Yoshikawa Patrick C Newman Tania Garron Robert L Atmar Clarence J Peters Robert B Couch |
| author_facet | Chien-Te Tseng Elena Sbrana Naoko Iwata-Yoshikawa Patrick C Newman Tania Garron Robert L Atmar Clarence J Peters Robert B Couch |
| author_sort | Chien-Te Tseng |
| collection | DOAJ |
| description | <h4>Background</h4>Severe acute respiratory syndrome (SARS) emerged in China in 2002 and spread to other countries before brought under control. Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated. Evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease.<h4>Design</h4>Four candidate vaccines for humans with or without alum adjuvant were evaluated in a mouse model of SARS, a VLP vaccine, the vaccine given to ferrets and NHP, another whole virus vaccine and an rDNA-produced S protein. Balb/c or C57BL/6 mice were vaccinated i.m. on day 0 and 28 and sacrificed for serum antibody measurements or challenged with live virus on day 56. On day 58, challenged mice were sacrificed and lungs obtained for virus and histopathology.<h4>Results</h4>All vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses. Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV. All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6) or given live virus, influenza vaccine, or PBS suggesting infection occurred in all. Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains. The pathologic changes seen in all control groups lacked the eosinophil prominence.<h4>Conclusions</h4>These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated. |
| format | Article |
| id | doaj-art-66f6819a9ae64dd6a9554ef487f9924c |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-66f6819a9ae64dd6a9554ef487f9924c2025-08-20T02:30:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3542110.1371/journal.pone.0035421Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus.Chien-Te TsengElena SbranaNaoko Iwata-YoshikawaPatrick C NewmanTania GarronRobert L AtmarClarence J PetersRobert B Couch<h4>Background</h4>Severe acute respiratory syndrome (SARS) emerged in China in 2002 and spread to other countries before brought under control. Because of a concern for reemergence or a deliberate release of the SARS coronavirus, vaccine development was initiated. Evaluations of an inactivated whole virus vaccine in ferrets and nonhuman primates and a virus-like-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologic-type lung disease.<h4>Design</h4>Four candidate vaccines for humans with or without alum adjuvant were evaluated in a mouse model of SARS, a VLP vaccine, the vaccine given to ferrets and NHP, another whole virus vaccine and an rDNA-produced S protein. Balb/c or C57BL/6 mice were vaccinated i.m. on day 0 and 28 and sacrificed for serum antibody measurements or challenged with live virus on day 56. On day 58, challenged mice were sacrificed and lungs obtained for virus and histopathology.<h4>Results</h4>All vaccines induced serum neutralizing antibody with increasing dosages and/or alum significantly increasing responses. Significant reductions of SARS-CoV two days after challenge was seen for all vaccines and prior live SARS-CoV. All mice exhibited histopathologic changes in lungs two days after challenge including all animals vaccinated (Balb/C and C57BL/6) or given live virus, influenza vaccine, or PBS suggesting infection occurred in all. Histopathology seen in animals given one of the SARS-CoV vaccines was uniformly a Th2-type immunopathology with prominent eosinophil infiltration, confirmed with special eosinophil stains. The pathologic changes seen in all control groups lacked the eosinophil prominence.<h4>Conclusions</h4>These SARS-CoV vaccines all induced antibody and protection against infection with SARS-CoV. However, challenge of mice given any of the vaccines led to occurrence of Th2-type immunopathology suggesting hypersensitivity to SARS-CoV components was induced. Caution in proceeding to application of a SARS-CoV vaccine in humans is indicated.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0035421&type=printable |
| spellingShingle | Chien-Te Tseng Elena Sbrana Naoko Iwata-Yoshikawa Patrick C Newman Tania Garron Robert L Atmar Clarence J Peters Robert B Couch Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS ONE |
| title | Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. |
| title_full | Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. |
| title_fullStr | Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. |
| title_full_unstemmed | Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. |
| title_short | Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. |
| title_sort | immunization with sars coronavirus vaccines leads to pulmonary immunopathology on challenge with the sars virus |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0035421&type=printable |
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