Scientists have made significant progress in developing an animal model of smallpox that closely resembles human disease, which will be necessary for testing of future vaccines and potential treatments.
The study, published in this week's online early edition of Proceedings of the National Academy of Sciences, is the first to demonstrate that variola virus, the causative agent of smallpox, can produce lethal disease in monkeys.
Smallpox, a devastating disease, was eradicated in 1979 through the efforts of the World Health Organization (WHO). Currently, infectious variola is known to exist only in two WHO-sanctioned repositories, one in Russia and the other at the Centers for Disease Control and Prevention (CDC) in Atlanta. However, there is concern that undisclosed reference stocks of the virus may exist, and the U.S. population is no longer routinely immunized against the disease. Due to its potential as an agent of bioterrorism, antiviral drugs and an improved smallpox vaccine are urgently needed.
Because the disease no longer occurs naturally, vaccine and drug candidates cannot be tested for their ability to prevent or treat smallpox in humans. Thus, licensing of future medical countermeasures for smallpox will depend upon animal studies. The U.S. Food and Drug Administration (FDA) has established an animal efficacy rule to facilitate the approval of vaccines and drugs for biological agents in cases where efficacy data in humans cannot be obtained.
In 1999, a study group convened by the U.S. Institute of Medicine recommended that variola research be conducted, and a research plan was approved by the WHO to develop an animal model of the disease. Peter B. Jahrling of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) led the research team.
Jahrling and his colleagues exposed 36 cynomolgous monkeys to one of two variola strains, Harper and India 7124. Eight animals were challenged by a combination of aerosol plus intravenous inoculation--four with Harper strain and four with India strain. The remaining 24 animals were exposed only by the intravenous route to varying doses of the virus.
Both variola strains produced severe disease, with almost uniform lethality and end-stage lesions resembling the human disease, in monkeys exposed by the combined route of infection. According to the authors, death usually occurred within six days of inoculation. Similar results were seen in monkeys that received the same dose of either virus by the intravenous route alone.