title: 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.
authors.affiliation: Department of Virology, Erasmus MC, 3000 DR Rotterdam, The Netherlands.
authors.forename: Koert J
authors.initials: KJ
authors.lastname: Stittelaar
authors.forename: Johan
authors.initials: J
authors.lastname: Neyts
authors.forename: Lieve
authors.initials: L
authors.lastname: Naesens
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.forename: Rob F
authors.initials: RF
authors.lastname: van Lavieren
authors.forename: Antonin
authors.initials: A
authors.lastname: Holý
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Niesters
authors.forename: Edwin
authors.initials: E
authors.lastname: Fries
authors.forename: Chantal
authors.initials: C
authors.lastname: Maas
authors.forename: Paul G H
authors.initials: PG
authors.lastname: Mulder
authors.forename: Ben A M
authors.initials: BA
authors.lastname: van der Zeijst
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D006801:Humans; D008252:Macaca fascicularis / Q000276:immunology* / Q000821:virology*; D045908:Mpox, Monkeypox / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D008993:Monkeypox virus / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity; D010100:Oxygen / Q000097:blood; D012900:Smallpox Vaccine / Q000008:administration & dosage / Q000276:immunology*; D015996:Survival Rate; D014611:Vaccination; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D012900:Smallpox Vaccine; D010100:Oxygen