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Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology

Chien-Te Tseng1,2, Elena Sbrana1 , Naoko Iwata-Yoshikawa1,2, Patrick C. Newman1 , Tania Garron1 , Robert L. Atmar3,4, Clarence J. Peters1,2, Robert B. Couch3,4* 1 Department of Microbiology and Immunology, The University of Texas Medical Branch, Galveston, Texas, United States of America, 2 Center for Biodefense and Emerging Disease, The University of Texas Medical Branch, Galveston, Texas, United States of America, 3 Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America, 4 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, United States of America.







Abstract Background: 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 viruslike-particle vaccine in mice induced protection against infection but challenged animals exhibited an immunopathologictype lung disease. Design: 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 IM 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. Results: 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. Conclusions: 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. Citation: Tseng C-T, Sbrana E, Iwata-Yoshikawa N, Newman PC, Garron T, et al. (2012) Immunization with SARS Coronavirus Vaccines Leads to Pulmonary Immunopathology on Challenge with the SARS Virus. PLoS ONE 7(4): e35421. doi:10.1371/journal.pone.0035421 Editor: Stefan Poehlmann, German Primate Center, Germany Received January 31, 2012; Accepted March 15, 2012; Published April 20, 2012 Copyright: 2012 Tseng et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Research performed by the authors and summarized in this report was supported by Public Health Service Contract NO1 AI 30039 from the National Institute of Allergy and Infectious Diseases. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: rcouch@bcm.edu

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