Development of Prophylactics and Therapeutics Against the Smallpox and Monkeypox Biothreat Agents

With the global eradication of smallpox in 1979, the causative agent, variola virus (VARV), no longer circulates in human populations; however, there is concern that clandestine stocks of VARV exist. The reintroduction of aerosolized VARV (or perhaps monkeypox virus [MPXV]) into human populations would result in high levels of mortality. The attractiveness of VARV as a bioweapon, and to a certain extent MPXV, is its inherent ability to spread from person-to-person. A natural threat also exists, as cases of human monkeypox are increasing in Africa, and for the first time human monkeypox was observed in the Western hemisphere during an outbreak in 2003. The threat posed by the intentional release of VARV or MPXV, or an MPXV epizoonosis will require a capacity to rapidly diagnose the disease and intervene therapeutically with antivirals. Intervention is likely to take place during the diagnosis of the first wave of cases approximately 10 to 15 days post-infection (p.i.). Preimmunization of “at-risk populations” with vaccines will likely not be practical, and circumstacial evidence suggests that the therapeutic use of vaccines is ineffective 4 days p.i. with VARV. Instead, immunization will be used to prevent further spread of the pathogen by treating at-risk populations. This chapter describes this threat and the processes for development of new orthopoxvirus vaccines and antivirals to meet it.