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Research Article

Vaccine Efficacy in Senescent Mice Challenged with Recombinant SARS-CoV Bearing Epidemic and Zoonotic Spike Variants

  • Damon Deming,

    Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Timothy Sheahan,

    Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Mark Heise,

    Affiliations: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Boyd Yount,

    Affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Nancy Davis,

    Affiliations: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Amy Sims,

    Affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Mehul Suthar,

    Affiliations: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Jack Harkema,

    Affiliation: Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States of America

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  • Alan Whitmore,

    Affiliation: Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Raymond Pickles,

    Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Ande West,

    Affiliation: Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Eric Donaldson,

    Affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Kristopher Curtis,

    Affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America

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  • Robert Johnston,

    Affiliations: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Ralph Baric mail

    To whom correspondence should be addressed. E-mail: rbaric@email.unc.edu

    Affiliations: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America

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  • Published: December 26, 2006
  • DOI: 10.1371/journal.pmed.0030525

About the Authors

Damon Deming, Timothy Sheahan, Mark Heise, Nancy Davis, Mehul Suthar, Raymond Pickles, Eric Donaldson, Robert Johnston, Ralph Baric
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Mark Heise, Nancy Davis, Mehul Suthar, Alan Whitmore, Ande West, Robert Johnston, Ralph Baric
Carolina Vaccine Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Mark Heise
Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Boyd Yount, Amy Sims, Ralph Baric
Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
Jack Harkema
Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan, United States of America
Kristopher Curtis
United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland, United States of America

Corresponding Author

Email: rbaric@email.unc.edu

Competing Interests

Experiments described in this manuscript use technology that ND helped develop at the University of North Carolina, and that has been licensed to AlphaVax, Inc., for commercial use. ND is a shareholder in AlphaVax, Inc.

Author Contributions

D. Deming, M. Heise, R. Johnston, and R. Baric designed the study. D. Deming, M. Heise, J. Harkema, A. Whitmore, R. Pickles, R. Johnston, and R. Baric analyzed the data. D. Deming, M. Heise, N. Davis, A. Sims, J. Harkema, R. Pickles, E. Donaldson, K. Curtis, R. Johnston, and R. Baric contributed to writing the paper. D. Deming, T. Sheahan, and B. Yount performed the SARS-CoV mice challenge experiments, the neutralization assays, and prepared tissue for titer and histopathology. T. Sheahan and B. Yount prepared virus using the SARS-CoV infectious cDNA system. K. Curtis, B. Yount, A. Whitmore, N. Davis, and A. West constructed and prepared the VRP vectors and to vaccinate and monitor mice. A. Sims and M. Suthar performed and analyzed the Western blot and in situ experiments, respectively. E. Donaldson generated the phylogenetic trees comparing SARS-CoV spike glycoprotein sequences and contributed to the design of the chimeric GDO3-S construct.