A New Layer of Medical Preparedness to Combat Emerging Infectious Disease

DARPA has selected five teams of researchers to support PREventing EMerging Pathogenic Threats (PREEMPT), a 3.5-year program first announced in January 2018 to reinforce traditional medical preparedness by containing viral infectious diseases in animal reservoirs and insect vectors before they can threaten humans. Through studies in secure laboratories and simulated natural environments, the PREEMPT researchers will model how viruses might evolve within animal populations, and assess the safety and efficacy of potential interventions. Autonomous Therapeutics, Inc., Institut Pasteur, Montana State University, The Pirbright Institute, and the University of California, Davis, lead the PREEMPT teams.

“DARPA challenges the PREEMPT research community to look far left on the emerging threat timeline and identify opportunities to contain viruses before they ever endanger humans,” said Dr. Brad Ringeisen, the DARPA program manager for PREEMPT. “One of the chief limitations of how infectious disease modeling is currently conducted is that it forecasts the trajectory of an outbreak only after it is underway in people. The best that data can do is inform a public health response, which places the United States in a reactive mode. We require proactive options to keep our troops and the homeland safe from emerging infectious disease threats.”

According to the World Health Organization (WHO), approximately 60 percent of emerging infectious diseases reported globally are zoonoses, meaning that they were initially diseases of animals and at some point became capable of infecting people. Zoonotic diseases are responsible for millions of human deaths every year, and the scope of the challenge is increasing due to the densification of livestock production, human encroachment into natural spaces, and upward trends in globalization, temperature, and population.

Ebola is a high-profile example of a zoonotic disease. Despite being relatively difficult to spread — requiring direct contact with fluids from infected organisms — a string of outbreaks over the past five years has highlighted the threat it could present once established in densely populated areas. Researchers express even greater concern over the pandemic potential of new strains of the influenza virus and other airborne pathogens. Even in the United States and its territories, where viruses do not frequently emerge directly from animal reservoirs, vector-borne transmission of zoonoses such as West Nile virus disease is on the rise.

The 2018 U.S. National Biodefense Strategy directs that it is essential to detect and contain such bio-threats, adopting a proactive posture to improve preparedness while also assessing and managing any biosecurity risks related to possible interventions. “The health of the American people depends on our ability to stem infectious disease outbreaks at their source, wherever and however they occur,” the document states. For the Department of Defense, that obligation extends to protection of deployed service members, who often operate in countries that are “hot spots” for emerging viruses yet lack robust public health infrastructure.

The teams DARPA selected for PREEMPT comprise multidisciplinary researchers who bring expertise and field experience from around the world, some of whom represent institutions from nations at high risk from emerging infectious disease. Institutions participating as sub-contractors to DARPA receive funding from the lead organizations except as otherwise noted.

The PREEMPT teams proposed to model specific diseases to assess the risk of spillover from animals into humans, identify key bottlenecks in the process as opportunities for intervention, and develop and assess novel, animal- or insect-focused interventions with built-in safety switches to prevent cross-species jump. The teams will collect samples from animal reservoirs in the field for analysis in secure, bio-contained facilities; some teams will also conduct analysis on existing banked samples and datasets. DARPA is not funding the release of PREEMPT interventions into the environment.

• Autonomous Therapeutics, Inc., under principal investigator Dr. Ariel Weinberger, leads a team made up of CSIRO Australian Animal Health Laboratory; Navy Medical Research Unit-2, funded directly by DARPA; University of California, Los Angeles; University of Chicago Medical School; and University of Texas Medical Branch. The team will study air-borne highly pathogenic avian influenza virus in birds and small mammals, and tick-borne Crimean-Congo hemorrhagic fever virus.
• The Center for Comparative Medicine and the One Health Institute at the University of California, Davis, under principal investigator Dr. Peter Barry and co-PI Dr. Brian Bird, respectively, lead a team made up of the Leibniz Institute for Experimental Virology; Mount Sinai School of Medicine; Rocky Mountain Laboratories of the National Institutes of Health (NIH), to be funded directly by DARPA; The Vaccine Group, Ltd., a spin-out of University of Plymouth; University of Glasgow; University of Idaho; and University of Western Australia. The team will examine Lassa virus spillover from rodents, and study Ebola virus in rhesus macaques.
• The Institut Pasteur, under principal investigator Dr. Carla Saleh, leads a team made up of Institut Pasteur International Network partners in Cambodia, Central African Republic, France, French Guiana, Madagascar, and Uruguay; Latham BioPharm Group; and Virginia Polytechnic Institute and State University. The team will study several mosquito-borne arboviruses, which refers broadly to animal or human viruses transmitted by insects, as well as mosquito-specific viruses that could interfere with arbovirus infection in the insect vector.
• Montana State University, under principal investigator Dr. Raina Plowright, leads a team made up of the Cary Institute of Ecosystem Studies; Colorado State University; Cornell University; Griffith University; Johns Hopkins University; NIH's Rocky Mountain Laboratories, funded directly by DARPA; Pennsylvania State University; Texas Tech University; University of California, Berkeley; University of California, Los Angeles; and University of Cambridge. The team will study henipavirus spillover from bats. The henipavirus genus of viruses contains multiple biothreat agents as categorized by NIH and the Centers for Disease Control and Prevention (CDC).
• The Pirbright Institute, under principal investigator Dr. Luke Alphey, leads a team made up of the University of Nottingham and the University of Tartu. The team seeks to disrupt mosquito transmission of flaviviruses, which include Dengue fever, West Nile, and Zika viruses.

Modeling and quantification are as important as new experimental technologies in preventing cross-species jumps. The results from modeling will inform when, where, and at what levels such interventions could be applied to achieve the greatest health benefits. Interventions under consideration include animal- or insect-targeted vaccines, therapeutic interfering particles, gene editors, and indirect approaches informed by environmental and ecological factors that affect how viruses are spread — for instance, understanding the environmental stressors that drive bats into closer contact with humans and devising mitigating options to reduce the likelihood of that contact.

The research teams' approaches each come with a unique set of potential benefits and challenges, and the teams are responsible for assessing and demonstrating to DARPA the safety, efficacy, stability, and controllability of their proposed interventions. In the future, these considerations could factor into decisions by the ultimate end users — communities, governments, and regulators — on which strategies to pursue to prevent new zoonoses.

DARPA and the PREEMPT teams receive guidance from independent expert advisors in the ethical, legal, social, and regulatory aspects of the life sciences. These individuals include Dr. Claudia Emerson, director of the Institute on Ethics & Policy for Innovation at McMaster University; Dr. Matt Kasper, legislative liaison for the U.S. Navy's Bureau of Medicine and Surgery, and a former deputy director of field laboratory operations at the Naval Medical Research Center; and Dr. Steve Monroe, associate director for Laboratory Science and Safety at the CDC, and a former deputy director of the CDC's National Center for Emerging and Zoonotic Infectious Diseases.

The teams also benefit from established relationships with local universities, communities, and governments based on prior or ongoing research. These relationships will facilitate initial field collection and help to familiarize stakeholders with PREEMPT technologies as they are being developed. DARPA is also beginning outreach to the WHO as a potential avenue for future transition of PREEMPT technologies.

DARPA intends that PREEMPT teams will perform fundamental research and publish results for review by the broader scientific community.

https://www.darpa.mil/news-events/2019-02-19