Nature 439, 745-748 (9 February 2006) | doi:10.1038/nature04295

Antiviral treatment is more effective than smallpox vaccination upon lethal monkeypox virus infection

Koert J. Stittelaar1, Johan Neyts3, Lieve Naesens3, Geert van Amerongen1,4, Rob F. van Lavieren5, Antonin Holý6, Erik De Clercq3, Hubert G. M. Niesters1, Edwin Fries1, Chantal Maas1, Paul G. H. Mulder2, Ben A. M. van der Zeijst4 and Albert D. M. E. Osterhaus1

There is concern that variola virus, the aetiological agent of smallpox, may be used as a biological weapon. For this reason several countries are now stockpiling (vaccinia virus-based) smallpox vaccine. Although the preventive use of smallpox vaccination has been well documented, little is known about its efficacy when used after exposure to the virus. Here we compare the effectiveness of (1) post-exposure smallpox vaccination and (2) antiviral treatment with either cidofovir (also called HPMPC or Vistide) or with a related acyclic nucleoside phosphonate analogue (HPMPO–DAPy) after lethal intratracheal infection of cynomolgus monkeys (Macaca fascicularis) with monkeypox virus (MPXV). MPXV causes a disease similar to human smallpox1 and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines2. We show that initiation of antiviral treatment 24 h after lethal intratracheal MPXV infection, using either of the antiviral agents and applying various systemic treatment regimens, resulted in significantly reduced mortality and reduced numbers of cutaneous monkeypox lesions. In contrast, when monkeys were vaccinated 24 h after MPXV infection, using a standard human dose of a currently recommended smallpox vaccine (Elstree-RIVM), no significant reduction in mortality was observed. When antiviral therapy was terminated 13 days after infection, all surviving animals had virus-specific serum antibodies and antiviral T lymphocytes. These data show that adequate preparedness for a biological threat involving smallpox should include the possibility of treating exposed individuals with antiviral compounds such as cidofovir or other selective anti-poxvirus drugs.

  1. Department of Virology and
  2. Department of Epidemiology and Biostatistics, Erasmus MC, 3000 DR Rotterdam, The Netherlands
  3. Rega Institute for Medical Research, K.U. Leuven, B-3000 Leuven, Belgium
  4. Netherlands Vaccine Institute, 3720 AL Bilthoven, The Netherlands
  5. ViroClinics B.V., 3000 DR Rotterdam, The Netherlands
  6. Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 16610 Prague 6, Czech Republic

Correspondence to: Albert D. M. E. Osterhaus1 Correspondence and requests for materials should be addressed to A.D.M.E.O. (Email: a.osterhaus@erasmusmc.nl).

Received 10 September 2005; Accepted 29 September 2005


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