Predicting the emergence of highly pathogenic viruses in animals and preventing them from spilling over to humans is the goal of a multimillion-dollar cooperative agreement from the Defense Advanced Research Projects Agency, or DARPA, with collaborating researchers at the University of California, Davis; the University of Idaho; and Plymouth University in England.

The up-to $9.37 million award will be used over 3½ years as part of DARPA’s Preventing Emerging Pathogenic Threats, or PREEMPT, program. PREEMPT seeks to improve medical preparedness, bolster the fight against emerging infectious disease and preserve the health of U.S. troops and communities around the world by containing high-risk zoonotic pathogens at their animal source.

“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,” said Brad Ringeisen, the DARPA program manager for PREEMPT. “We require proactive options to keep our troops and the homeland safe from emerging infectious disease threats.”

Led by the One Health Institute in the UC Davis School of Veterinary Medicine and the Center for Comparative Medicine in the UC Davis schools of Medicine and Veterinary Medicine, the research team will concentrate efforts on Lassa virus and Ebola virus. These two infectious and often fatal zoonotic viruses present significant biological threats to deployed military personnel, local communities in West and Central Africa, and global health security.

From reactive to proactive

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 begin collecting and testing samples from Mastomys rats, a widespread local rodent and known reservoir for Lassa virus. The virus causes Lassa fever, an acute viral hemorrhagic illness endemic throughout West Africa.

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 USAID-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 Lassa virus emergence and spillover into people.

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

Potential game changer

In the second phase, researchers will design and test a novel vaccine in collaboration with The Vaccine Group and the Leibniz Institute for Experimental Virology. Testing will occur exclusively in contained, biosecure facilities.

“A vaccine designed for broad uptake within a specific animal community could be a game changer,” said Peter Barry, co-principal investigator and professor emeritus with UC Davis Center for Comparative Medicine. “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.”

A track record of success

The project team reflects broad expertise in field pathogen detection, disease dynamics and cytomegalovirus biology.

At UC Davis, the One Health Institute has been integral in global surveillance of zoonotic disease and capacity building through its leadership of PREDICT, a project that aims to find viruses before they spill over into humans. Last year, 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 Center for Comparative Medicine brings 20 years of research excellence in animal modeling of human diseases to the project. 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 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 Michael Lairmore, dean of the UC Davis School of Veterinary Medicine. “PREEMPT exemplifies the level of innovation that’s possible using a One Health approach, and it will protect lives on a global scale.”

In addition to Barry and Bird, the other co-principal investigators are Michael Jarvis, associate professor at Plymouth University’s School of Biomedical Sciences, from The Vaccine Group; and Professor Scott Nuismer from the University of Idaho.

Co-investigators include researchers Wolfram Brune of the Leibniz Institute for Experimental Virology in Germany; Andrew Davison of the University of Glasgow in Scotland; and Alec Redwood of the University of Western Australia.