PUBLIC HEALTHAction Needed to Improve U.S. Smallpox Readiness and Diagnostics, Vaccines, and Therapeutics: Report

A new report from the National Academies of Sciences, Engineering, and Medicine says that action is needed to enhance U.S. readiness for smallpox and related diseases, as well as to improve diagnostics, vaccines, and therapeutics that could be used in case of an outbreak. The COVID-19 pandemic revealed weaknesses in the ability of U.S. public health and health care systems to adapt and respond to an unfamiliar pathogen, as did challenges during the recent mpox outbreak to rapidly making diagnostics, vaccines, and therapeutics available at scale.

The development of better diagnostics, vaccines, and therapeutics — also called medical countermeasures — would improve the nation’s ability to respond to a smallpox outbreak or attack using the virus, the report says. It also calls for strengthening the systems and policies that would allow public health and health care systems to act quickly and effectively, such as those that could support rapid distribution of a vaccine.

The report says U.S. population changes and advancements in gene editing and synthesis technologies have drastically altered the potential for a smallpox outbreak or attack in recent years. It is now possible to engineer variola virus, the virus that causes smallpox, raising the possibility of accidental or intentional release. Furthermore, illnesses related to smallpox such as mpox, Alaskapox, and cowpox are increasingly found in humans, presenting the need for medical countermeasures that can detect, treat, and prevent these diseases.

In 1980, the World Health Assembly declared smallpox eradicated, and no naturally occurring smallpox cases have been reported since that time. Two WHO sanctioned collections of the live variola virus — at the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia, and the Laboratory for Applied Microbiology at Koltsovo in Russia — store samples and use variola virus in research. Viruses related to variola, called orthopoxviruses, are also used in research.  

Research using live variola and related viruses is essential for creating and improving medical countermeasures for smallpox and other related diseases, and to ensuring the U.S. is ready to respond to an outbreak, says the report. Live variola in particular is essential for developing new targets for more effective therapeutics; verifying the efficacy of vaccines, treatments, and diagnostics for smallpox; and creating animal models that can be used in research in place of humans. Research using these viruses can also fill gaps in our fundamental understanding of orthopoxvirus biology, ecology, evolution, transmission, and disease onset in humans.