A Double-Inactivated Severe Acute Respiratory Syndrome Coronavirus Vaccine Provides Incomplete Protection in Mice and Induces Increased Eosinophilic Proinflammatory Pulmonary Response upon Challenge

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  • Meagan Bolles
    • Other Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • Damon Deming
    • Other Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • Kristin Long
    • Other Affiliation: Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • Sudhakar Agnihothram
    • Other Affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • Alan Whitmore
    • Other Affiliation: Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • Martin Ferris
    • Other Affiliation: Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • William Funkhouser
    • Other Affiliation: Department of Pathology, University of North Carolina School of Medicine, Chapel Hill, North Carolina
  • Lisa Gralinski
    • Other Affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • Allison Totura
    • Other Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • Mark Heise
    • Other Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina ; Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina ; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  • Ralph S. Baric
    • Other Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina ; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
Abstract
  • Severe acute respiratory syndrome coronavirus (SARS-CoV) is an important emerging virus that is highly pathogenic in aged populations and is maintained with great diversity in zoonotic reservoirs. While a variety of vaccine platforms have shown efficacy in young-animal models and against homologous viral strains, vaccine efficacy has not been thoroughly evaluated using highly pathogenic variants that replicate the acute end stage lung disease phenotypes seen during the human epidemic. Using an adjuvanted and an unadjuvanted double-inactivated SARS-CoV (DIV) vaccine, we demonstrate an eosinophilic immunopathology in aged mice comparable to that seen in mice immunized with the SARS nucleocapsid protein, and poor protection against a nonlethal heterologous challenge. In young and 1-year-old animals, we demonstrate that adjuvanted DIV vaccine provides protection against lethal disease in young animals following homologous and heterologous challenge, although enhanced immune pathology and eosinophilia are evident following heterologous challenge. In the absence of alum, DIV vaccine performed poorly in young animals challenged with lethal homologous or heterologous strains. In contrast, DIV vaccines (both adjuvanted and unadjuvanted) performed poorly in aged-animal models. Importantly, aged animals displayed increased eosinophilic immune pathology in the lungs and were not protected against significant virus replication. These data raise significant concerns regarding DIV vaccine safety and highlight the need for additional studies of the molecular mechanisms governing DIV-induced eosinophilia and vaccine failure, especially in the more vulnerable aged-animal models of human disease.
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  • Article
Rights statement
  • In Copyright
Journal title
  • Journal of Virology
Journal volume
  • 85
Journal issue
  • 23
Page start
  • 12201
Page end
  • 12215
Language
  • English
ISSN
  • 0022-538X
  • 1070-6321
  • 1098-5514
Publisher
  • American Society for Microbiology

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