Prophecy

Military readiness and national security depend on the health and wellbeing of military servicemembers. The Department of Defense’s (DoD) cumulative investment in personnel comprises the second-largest share of the total defense budget. As such, DoD seeks advances in healthcare to ensure warfighters can operate at peak performance, and by focusing on prevention DoD may contain costs while enhancing readiness. In this context, the Prophecy (Pathogen Defeat) program will explore the evolution of viruses in the hopes of predicting viral mutations and ultimately developing drugs and vaccines in advance of need.

According to the National Institute of Allergy and Infectious Diseases, in the past 20 years, out of the newly recognized pathogens that impact human and animal health, approximately 44 percent are viruses. (1) Many of these pathogens, particularly RNA viruses, are characterized by a high mutation rate that allows them to rapidly adapt to a changing environment, as occurred in the 2009 H1N1 pandemic. Additionally, many viruses undergo more widespread genetic events (e.g., rearrangements, reassortments) that significantly alter the viral genome. These changes can produce virions capable of evading existing vaccine-acquired and convalescent immunity in humans and animals.

Current antiviral agents and vaccines are designed to protect against viruses that are already endemic, virulent and medically significant to human or animal health. Today’s antiviral therapy research-and-development cycle is reactive in posture, with new vaccines requiring months and new small-molecule inhibitors requiring years to counter emerging viruses.

With the exception of limited influenza viral-forecasting based on uneven global statistics, there is presently no reliable capability to predict viral reassortment or mutations responsible for the emergence of new viral strains. This capability gap leaves the military vulnerable to the detrimental health effects of future viral strains, and thus poses a significant risk to assured military readiness.

The Prophecy program seeks to transform the vaccine and drug development enterprise from observational and reactive to predictive and preemptive by spurring development of a multidisciplinary approach to predicting viral evolution. To achieve this objective, the three-phased program will focus on: 1) development of a viral-evolution platform for generating datasets used to build and validate algorithms predictive of viral evolution; 2) refinement of the platform to include mechanisms capable of controlling multiple selective pressures and accompanying predictive evolutionary models and algorithms; and 3) testing and validation of the system and algorithms using multiple selective pressures on at least three closely related virus strains in an experimental setting. Phase III will to attempt to replicate in a laboratory the viral mutations or evolutions that are documented to have occurred naturally.

References:

• United States Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases (April 2011). List of NIAID Emerging and Re-emerging Diseases. Washington, DC: U.S. Department of Health and Human Services. Retrieved March 15, 2012 from http://www.niaid.nih.gov/topics/emerging/pages/list.aspx.