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Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox

Nature volume 428, pages 182–185 (2004)Cite this article

Abstract

The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they or their contacts have increased susceptibility to severe vaccine side effects1. As vaccines can no longer be tested for their ability to prevent smallpox, licensing will necessarily include comparative immunogenicity and protection studies in non-human primates. Here we compare the highly attenuated modified vaccinia virus Ankara (MVA)2 with the licensed Dryvax vaccine in a monkey model. After two doses of MVA or one dose of MVA followed by Dryvax, antibody binding and neutralizing titres and T-cell responses were equivalent or higher than those induced by Dryvax alone. After challenge with monkeypox virus, unimmunized animals developed more than 500 pustular skin lesions and became gravely ill or died, whereas vaccinated animals were healthy and asymptomatic, except for a small number of transient skin lesions in animals immunized only with MVA.

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Figure 1: Sizes of Dryvax-induced lesions.
Figure 2: Binding and vaccinia virus neutralizing antibody responses.
Figure 3: Induction of vaccinia-virus-specific IFN-γ-producing T cells.
Figure 4: Viral load following monkeypox virus challenge.

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Acknowledgements

We are grateful to R. Elkins (NIAID) for animal acquisition and to R. Byrum (Bioqual, Inc.) for animal care and immunizations. The work was supported by the National Institute of Allergy and Infectious Diseases.

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Authors and Affiliations

  1. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892-0445, USA

    Patricia L. Earl, Jeffrey L. Americo, Linda S. Wyatt & Bernard Moss

  2. Henry M. Jackson Foundation, Rockville, Maryland, 20850, USA

    Leigh Anne Eller

  3. Schools of Dental and Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA

    J. Charles Whitbeck, Gary H. Cohen & Roselyn J. Eisenberg

  4. United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, 21702-5011, USA

    Christopher J. Hartmann, David L. Jackson, David A. Kulesh, Mark J. Martinez, David M. Miller, Eric M. Mucker, Joshua D. Shamblin, Susan H. Zwiers, John W. Huggins & Peter B. Jahrling

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Correspondence to Bernard Moss.

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The authors declare that they have no competing financial interests.

Supplementary information

Supplementary Figure 1

Photographs of Dryvax-induced skin lesions. (PDF 551 kb)

Supplementary Figure 2

Antibody responses of individual animals. (PDF 78 kb)

Supplementary Figure 3

Reduction of cell-to-cell spread of vaccinia virus by sera fromindividual animals. (PDF 195 kb)

Supplementary Figure 4

Monkeypox viral skin lesions. (PDF 47 kb)

Supplementary Figure Legends (PDF 25 kb)

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Earl, P., Americo, J., Wyatt, L. et al. Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox. Nature 428, 182–185 (2004). https://doi.org/10.1038/nature02331

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