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Clonal vaccinia virus grown in cell culture as a new smallpox vaccine

Nature Medicine volume 9, pages 1125–1130 (2003)Cite this article

Abstract

Although the smallpox virus was eradicated over 20 years ago, its potential release through bioterrorism has generated renewed interest in vaccination. To develop a modern smallpox vaccine, we have adapted vaccinia virus that was derived from the existing Dryvax vaccine for growth in a human diploid cell line. We characterized six cloned and one uncloned vaccine candidates. One clone, designated ACAM1000, was chosen for development based on its comparability to Dryvax when tested in mice, rabbits and monkeys for virulence and immunogenicity. By most measures, ACAM1000 was less virulent than Dryvax. We compared ACAM1000 and Dryvax in a randomized, double-blind human clinical study. The vaccines were equivalent in their ability to produce major cutaneous reactions ('takes') and to induce neutralizing antibody and cell-mediated immunity against vaccinia virus.

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Figure 1: Characterization of vaccine candidates.
Figure 2: Survival of suckling mice after intracerebral inoculation with ACAM1000 or Dryvax.
Figure 3: Immunogenicity of ACAM1000 in mice.
Figure 4: Cellular immune responses in clinical trial subjects.

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Acknowledgements

We thank G. Drabik, T. Farrell, K. Georgakopoulos, J. Hamberger, Y. Liu, P. Papastathis and S. Pougatcheva (Acambis) for expert technical assistance; N. Tobin and E. Gove (Acambis) for animal care; D. Vellom (Acambis) for purification method development; T. Kemp and S. Woodward (Acambis) and D. Mathis (PRA International) for clinical trial assistance; W. T. Archambault (Virtu Stat) for statistical advice; R. McAvoy (Acambis) for contract management; I. Levenbook for neuropathological evaluation of monkey tissues; and J. Gilly and P. Lyons (BioReliance) for vaccine manufacturing and testing. We also thank J. Becher, J. W. LeDuc, J. Esposito and L. Falgiano (CDC) and P. K. Russell and D.A. Henderson (US Department of Health and Human Services) for advice and support. This work was supported by contract number 200-2000-00001 from the CDC. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the United States Government.

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Authors and Affiliations

  1. Acambis Inc., 38 Sidney Street, Cambridge, 02139, Massachusetts, USA

    Richard Weltzin, Jian Liu, Konstantin V Pugachev, Gwendolyn A Myers, Brie Coughlin, Paul S Blum, Richard Nichols & Thomas P Monath

  2. PRA International, 16300 College Boulevard, Lenexa, 66219, Kansas, USA

    Casey Johnson

  3. Center for Infectious Disease & Vaccine Research, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, 01655, Massachusetts, USA

    John Cruz, Jeffrey S Kennedy & Francis A Ennis

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  1. Richard Weltzin
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Correspondence to Richard Weltzin or Thomas P Monath.

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Competing interests

R.W., J.L., K.V.P., G.A.M., B.C., P.S.B., R.N. & T.M. are employees of Acambis Inc., which manufactures the ACAM1000 vaccine, and as such own stock or have been granted stock options in Acambis Inc.

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Weltzin, R., Liu, J., Pugachev, K. et al. Clonal vaccinia virus grown in cell culture as a new smallpox vaccine. Nat Med 9, 1125–1130 (2003). https://doi.org/10.1038/nm916

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