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Smallpox vaccine–induced antibodies are necessary and sufficient for protection against monkeypox virus

Nature Medicine volume 11, pages 740–747 (2005)Cite this article

Abstract

Vaccination with live vaccinia virus affords long-lasting protection against variola virus, the agent of smallpox. Its mode of protection in humans, however, has not been clearly defined. Here we report that vaccinia-specific B-cell responses are essential for protection of macaques from monkeypox virus, a variola virus ortholog. Antibody-mediated depletion of B cells, but not CD4+ or CD8+ T cells, abrogated vaccine-induced protection from a lethal intravenous challenge with monkeypox virus. In addition, passive transfer of human vaccinia-neutralizing antibodies protected nonimmunized macaques from severe disease. Thus, vaccines able to induce long-lasting protective antibody responses may constitute realistic alternatives to the currently available smallpox vaccine (Dryvax).

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Figure 1: Depletion of B cells and CD8+ T lymphocytes in rhesus macaques.
Figure 2: Humoral immune response in the treated macaques.
Figure 3: Vaccinia antibodies and CD4+ T cells in protection from monkeypox virus.

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Acknowledgements

Thanks to S. Snodgrass for editorial assistance; M. Zanetti, B. Murphy and M. Martin for critical review of the manuscript; S. Gurunathan and B. Golding for helpful discussion; MedImmune, Centocor and Johnson & Johnson for providing access to monoclonal antibodies; T. Unangst, A. Cristillo, J. Bassler and V. Livingston for flow cytometry; S. Sloane for monkeypox DNA PCRs; E. Thompson for immunoprecipitation assays; and P. Markham, S. Orndorff, J. Treece, J. Parrish, J. Wells and P. Silvera for assistance with the animals. We also are very grateful to P. Jahrling and J. Huggins for providing the stock of the Zaire 79 strain. Reagents used in this study were provided by the US National Institutes of Health Nonhuman Primate Reagent Resource (RR016001, AI040101) and produced by the National Cell Culture Center.

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Authors and Affiliations

  1. Animal Models & Retroviral Vaccines Section, National Cancer Institute, 41/D804, Bethesda, 20892, Maryland, USA

    Yvette Edghill-Smith & Genoveffa Franchini

  2. Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, 29/232, HFM-345, Bethesda, 20892, Maryland, USA

    Hana Golding, Jody Manischewitz & Lisa R King

  3. Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, 29/232, HFM-345, Bethesda, 20892, Maryland, USA

    Dorothy Scott

  4. Biodefense Clinical Research Branch, Office of Clinical Research, National Institute of Allergy and Infectious Diseases, Bethesda, 20892, Maryland, USA

    Mike Bray

  5. Southern Research Institute, 431 Aviation Way, Frederick, 21701, Maryland, USA

    Aysegul Nalca

  6. Virology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, 21702, Maryland, USA

    Jay W Hooper & Chris A Whitehouse

  7. Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE-113, 330 Brookline Avenue, Boston, 02215, Massachusetts, USA

    Joern E Schmitz & Keith A Reimann

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  1. Yvette Edghill-Smith
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Correspondence to Genoveffa Franchini.

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Edghill-Smith, Y., Golding, H., Manischewitz, J. et al. Smallpox vaccine–induced antibodies are necessary and sufficient for protection against monkeypox virus. Nat Med 11, 740–747 (2005). https://doi.org/10.1038/nm1261

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