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

Abstract
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 smallpox and this animal model can be used to measure differences in the protective efficacies of classical and new-generation candidate smallpox vaccines. 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.
AuthorsKoert J Stittelaar, Johan Neyts, Lieve Naesens, Geert van Amerongen, Rob F van Lavieren, Antonin Holý, Erik De Clercq, Hubert G M Niesters, Edwin Fries, Chantal Maas, Paul G H Mulder, Ben A M van der Zeijst, Albert D M E Osterhaus
JournalNature (Nature) Vol. 439 Issue 7077 Pg. 745-8 (Feb 09 2006) ISSN: 1476-4687 [Electronic] England
PMID16341204 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antiviral Agents
  • Smallpox Vaccine
  • Oxygen
Topics
  • Animals
  • Antiviral Agents (pharmacology, therapeutic use)
  • Cell Line
  • Humans
  • Macaca fascicularis (immunology, virology)
  • Monkeypox (blood, drug therapy, immunology, virology)
  • Monkeypox virus (drug effects, immunology, pathogenicity)
  • Oxygen (blood)
  • Smallpox Vaccine (administration & dosage, immunology)
  • Survival Rate
  • Vaccination
  • Viral Load

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