Smallpox (Variola virus) is considered a high-priority biological threat agent. It can be spread using an aerosol spray, transmitted from person to person via close contact, and can survive in the environment up to one day, depending on ambient conditions. The fatality rate following infection is high, and there is no effective, approved treatment. Routine smallpox vaccination ended in the U.S. in 1972. Those who received the vaccination may experience a reduction in symptom severity and a decreased mortality rate, however, the infection rate and spread of disease amongst the general population is expected to be high.
On September 23, 2004, the Secretary of Homeland Security determined that the smallpox virus is a material threat to the U.S. population sufficient to affect national security. Because the threat is credible and smallpox has the potential to cause significant casualties and massive disruption of political, economic, and social infrastructures in the U.S., strong efforts to reduce U.S. vulnerability to smallpox are warranted. As such, BARDA is supporting the development of both vaccines and antivirals that can protect against or treat smallpox. An effective antiviral treatment could mitigate the effects of smallpox disease. It is likely that such an antiviral may also be effective against other pox viruses.
Under the Project BioShield Act (2004) (PDF - 191 KB), Pandemic and All-Hazards Preparedness Act (2006) (PDF -248 KB), and Pandemic and All-Hazards Reauthorization Act (2013) (PDF - 284 KB), BARDA’s strategy to support advanced development and procurement of critical medical countermeasures (MCMs) targets biothreats that have been determined by the Department of Homeland Security (DHS) as Material Threats. BARDA’s Smallpox Antiviral Program supports advanced development, procurement and stockpiling of variola major (smallpox) countermeasures for use in treating symptomatic smallpox. DHS issued a Material Threat Determination for smallpox in 2004, establishing it as a threat to national security. The Public Health Emergency Medical Countermeasure Enterprise (PHEMCE)
BARDA has transitioned two antiviral drugs candidates—ST-246 (SIGA) and brincidofovir (Chimerix)—from NIH into advanced development and procurement under Project BioShield. ST-246 was procured under Project Bioshield in 2011 and delivered to the Strategic National Stockpile (SNS), where it remains available for use under a CDC or DoD contingency IND or under Emergency Use Authorization. Brincidofovir is being developed for the treatment of smallpox, as well as for the treatment of cytomegalovirus and adenovirus infections associated with bone marrow transplantation. In addition to oral formulations of each drug, BARDA’s Smallpox Antiviral Program is supporting the development of a liquid suspension formulation of brincidofovir and a sprinkle formulation of ST-246 for special populations, including pediatric patients and individuals who are unable to swallow pills.
BARDA is working towards meeting PHEMCE requirements for two antivirals with different mechanisms of action available to mitigate emergence of potential drug resistance. The smallpox antiviral drugs, in combination with the smallpox vaccines already stockpiled, will comprise a robust armamentarium of medical countermeasures to smallpox. With continuing development and regulatory approval of new diagnostic platform technologies through support from programs like Innovations and Biothreat Diagnostics, BARDA is improving our ability to rapidly detect and treat biothreats like smallpox in the entire U.S. population.
Under the Project BioShield Act (2004) (PDF - 191 KB), Pandemic and All-Hazards Preparedness Act (2006) (PDF -248 KB), and Pandemic and All-Hazards Reauthorization Act (2013) (PDF - 284 KB), BARDA’s strategy to support advanced development and procurement of critical medical countermeasures (MCMs) targets biothreats that have been determined by the Department of Homeland Security as Material Threats. BARDA’s Smallpox Vaccine Program focuses on maintaining sustainable and cost-effective vaccine stockpile capacity, with a goal of having enough smallpox vaccine for the entire Nation. This includes a vaccine for the general population and a vaccine for “at-risk”individuals (potentially contraindicated for a live replicating vaccine), complemented by antivirals with different mechanisms of action to treat individuals symptomatic with disease and by vaccinia immune globulin to treat adverse events associated with vaccination. This combination of MCMs will prepare the PHEMCE to appropriately respond to a smallpox incident.
BARDA’s Smallpox Vaccines Program has supported advanced development of a third generation smallpox vaccine, IMVAMUNE® [smallpox Modified Vaccinia Ankara (MVA) vaccine], for “at-risk” individuals to augment the vaccine for the general population. BARDA’s strategic goals for this vaccine candidate have focused on late stage development in support of potential licensure of IMVAMUNE®, and procurement under Project BioShield for delivery to the Strategic National Stockpile (SNS). The current liquid frozen formulation of IMVAMUNE® is available under Emergency Use Authorization (EUA) during a declared emergency to special populations, including HIV+ persons and individuals with atopic dermatitis; to include all age ranges, pregnant women and/or nursing mothers.
BARDA also is funding the advanced development of a lyophilized formulation of IMVAMUNE® that may have a significantly longer shelf life and easier cold chain logistics for storage and administration compared to its liquid frozen counterpart. Positive outcomes of the lyophilized formulation may include a reduction in total lifecycle management costs and a more sustainable stockpile of smallpox vaccine for immunocompromised individuals. The stockpiling and continued development of IMVAMUNE® ensures that the U.S. Government has a robust capability to vaccinate a diverse population during a smallpox emergency. In combination with BARDA’s antiviral development efforts, the Smallpox Vaccine Program has strengthened the current MCM armamentaria necessary to respond to a smallpox event.