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.