Pre-empting zoonotic disease threats

A multimillion-dollar Defense Department grant is helping veterinary researchers predict the emergence of highly pathogenic zoonotic viruses and prevent them spilling over to humans.

In February, the Defense Advanced Research Projects Agency announced an agreement with scientists at the University of California-Davis, the University of Idaho, and Plymouth University in England to work on the agency's Preventing Emerging Pathogenic Threats program. DARPA has committed up to $9.37 million in support for the program over 3 1/2 years.

With U.S. military forces deploying throughout the world, the Defense Department's PREEMPT program is designed to preserve military readiness by protecting troops from infectious diseases. Instead of treating people, PREEMPT focuses on animal reservoirs and insect vectors where viral pathogens originate.

"DARPA challenges the PREEMPT research community to look far earlier on the emerging threat timeline and identify opportunities to contain viruses before they ever endanger humans," explained Brad Ringeisen, PhD, the agency's program manager for PREEMPT, in a press release. "We require proactive options to keep our troops and the homeland safe from emerging infectious disease threats."

DARPA was established by the Eisenhower administration in 1958 in response to the Soviet launch of Sputnik 1 the previous year. For the past several decades, the agency has been responsible for developing emerging technologies for the U.S. military.

The PREEMPT research team, led by the One Health Institute at the UC-Davis School of Veterinary Medicine and the Center for Comparative Medicine at the UC-Davis School of Medicine and veterinary school, will concentrate efforts on the Lassa and Ebola viruses. Both zoonotic viruses are seen as significant biological threats to deployed military personnel, local communities in West and Central Africa, and global health security.

Despite a worldwide investment of time and resources, the ability to predict with certainty which viruses will make the zoonotic jump into humans remains elusive. As a result, responses to outbreaks have been reactive, with the focus on containing the spread of virus through behavior change and treating or vaccinating people infected after the initial spillover.

The first phase of the project is underway in Sierra Leone. Field teams will collect and test samples from Mastomys rats, a widespread local rodent and known reservoir for Lassa virus.

The team works closely with the Sierra Leone government, University of Makeni, Njala University, and community partners, leveraging relationships established over the past five years through the U.S. Agency for International Development–funded Predict project, also headquartered at the UC-Davis One Health Institute.

Researchers will integrate data from the field studies, along with viral testing and probability models, to predict the real-time risk for the emergence of Lassa virus and spillover into people.

"PREEMPT takes a deep dive into Lassa virus and its ecology," said Dr. Brian Bird, co-principal investigator of the PREEMPT project and global lead of Predict-Sierra Leone, in the press release. "We want to understand why one particular variant of the virus spills over into people versus another."

In the program's second phase, researchers will design and test a novel vaccine in collaboration with The Vaccine Group and the Leibniz Institute for Experimental Virology.

"A vaccine designed for broad uptake within a specific animal community could be a game changer," said Peter Barry, PhD, co-principal investigator and professor emeritus with UC-Davis Center for Comparative Medicine, in the press release. "If we can disrupt the spread of a virus within an animal community, we will help to eliminate the threat of animal diseases ultimately spilling over into humans."

The One Health Institute has been integral in global surveillance of zoonotic disease and capacity building through its leadership of Predict. In 2018, the Predict team announced the discoveries of a new species of ebolavirus and a closely related cousin, Marburg virus, in bats in Sierra Leone prior to those viruses ever being detected in a sick human or animal.

The PREEMPT team's plan to use cytomegalovirus, a common virus, to vaccinate animals against other viruses, such as Lassa virus and Ebola virus, is a direct result of work initiated by Dr. Barry to develop a nonhuman primate model of human cytomegalovirus.

"This type of collaboration across disciplines made possible through this DARPA cooperative agreement is how we'll get in front of the unpredictable nature of zoonotic diseases," said Dr. Michael Lairmore, dean of the UC-Davis School of Veterinary Medicine, in the press release. "PREEMPT exemplifies the level of innovation that's possible using a One Health approach, and it will protect lives on a global scale."

Related JAVMA content:

Global project aims to identify viral threats (May 1, 2018)

Hunting for novel viruses (Jan. 15, 2015)

California global health institute established (Jan. 1, 2010)

U.S. makes big push to prevent global pandemic (Dec. 1, 2009)