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PLoS ONE. Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model

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  • PLoS ONE. Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model

    [Source: PLoS ONE, full page: (LINK). Abstract, edited.]
    Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model


    Mark J. Cameron<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP>, Alyson A. Kelvin<SUP>10</SUP>, Alberto J. Leon<SUP>1</SUP><SUP>,</SUP><SUP>5</SUP>, Cheryl M. Cameron<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP>, Longsi Ran<SUP>1</SUP>, Luoling Xu<SUP>1</SUP>, Yong-Kyu Chu<SUP>6</SUP>, Ali Danesh<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>,</SUP><SUP>4</SUP>, Yuan Fang<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>,</SUP><SUP>4</SUP>, Qianjun Li<SUP>6</SUP>, Austin Anderson<SUP>6</SUP>, Ronald C. Couch<SUP>7</SUP>, Stephane G. Paquette<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>,</SUP><SUP>3</SUP>, Ndingsa G. Fomukong<SUP>7</SUP>, Otfried Kistner<SUP>8</SUP>, Manfred Lauchart<SUP>8</SUP>, Thomas Rowe<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP>, Kevin S. Harrod<SUP>7</SUP>, Colleen B. Jonsson<SUP>9</SUP>, David J. Kelvin<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>,</SUP><SUP>3</SUP><SUP>,</SUP><SUP>4</SUP><SUP>,</SUP><SUP>5</SUP><SUP>,</SUP><SUP>7</SUP><SUP>,</SUP><SUP>11</SUP><SUP>*</SUP>
    <SUP></SUP>
    1 Division of Experimental Therapeutics, Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada, 2 University of Toronto, Toronto, Ontario, Canada, 3 Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada, 4 Department of Immunology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada, 5 International Institute of Infection and Immunity, Shantou University Medical College, Shantou, Guangdong, China, 6 Department of Biochemistry and Molecular Biology, Southern Research Institute, Birmingham, Alabama, United States of America, 7 Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America, 8 Baxter Innovations GmbH, Vienna, Austria, 9 Center for Predictive Medicine, Louisville, Kentucky, United States of America, 10 Immune Diagnostics & Research, Toronto, Ontario, Canada, 11 Sezione di Microbiologia Sperimentale e Clinica, Dipartimento di Scienze Biomediche, Universit? degli Studi di Sassari, Sassari, Italy



    Abstract

    In terms of its highly pathogenic nature, there remains a significant need to further define the immune pathology of SARS-coronavirus (SARS-CoV) infection, as well as identify correlates of immunity to help develop vaccines for severe coronaviral infections. Here we use a SARS-CoV infection-reinfection ferret model and a functional genomics approach to gain insight into SARS immunopathogenesis and to identify correlates of immune protection during SARS-CoV-challenge in ferrets previously infected with SARS-CoV or immunized with a SARS virus vaccine. We identified gene expression signatures in the lungs of ferrets associated with primary immune responses to SARS-CoV infection and in ferrets that received an identical second inoculum. Acute SARS-CoV infection prompted coordinated innate immune responses that were dominated by antiviral IFN response gene (IRG) expression. Reinfected ferrets, however, lacked the integrated expression of IRGs that was prevalent during acute infection. The expression of specific IRGs was also absent upon challenge in ferrets immunized with an inactivated, Al(OH)<SUB>3</SUB>-adjuvanted whole virus SARS vaccine candidate that protected them against SARS-CoV infection in the lungs. Lack of IFN-mediated immune enhancement in infected ferrets that were previously inoculated with, or vaccinated against, SARS-CoV revealed 9 IRG correlates of protective immunity. This data provides insight into the molecular pathogenesis of SARS-CoV and SARS-like-CoV infections and is an important resource for the development of CoV antiviral therapeutics and vaccines.



    Citation: Cameron MJ, Kelvin AA, Leon AJ, Cameron CM, Ran L, et al. (2012) Lack of Innate Interferon Responses during SARS Coronavirus Infection in a Vaccination and Reinfection Ferret Model. PLoS ONE 7(9): e45842. doi:10.1371/journal.pone.0045842

    Editor: Volker Thiel, Kantonal Hospital St. Gallen, Switzerland

    Received: April 5, 2012; Accepted: August 23, 2012; Published: September 24, 2012

    Copyright: ? 2012 Cameron 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: This study was supported by the Canadian Institutes of Health Research (CIHR), and Baxter Innovations GmbH and the National Institutes of Health and National Institute of Allergy and Infectious Disease (NIH/NIAID) through Contract No. N01-AI-30063 Task Order No. 03. The CIHR and NIH/NIAID had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Baxter supplied the SARS vaccine and were involved in the design of vaccination study.

    Competing interests: Otfried Kistner and Manfred Lauchart work for Baxter and supplied the SARS vaccine and were involved in the design of vaccination study. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.


    * E-mail: dkelvin@uhnres.utoronto.ca
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