Vanderbilt University Medical Center is working with the U.S. Department of Defense (DOD) in an expanded effort to rapidly develop monoclonal antibodies that can defend against emerging infections and other critical biological threats and possibly prevent the next pandemic.
In June, James Crowe Jr., MD, Robert Carnahan, PhD, and colleagues in the Vanderbilt Vaccine Center (VVC) began an “antibody sprint” to test how quickly they can develop neutralizing monoclonal antibodies against hantaviruses, potentially lethal viruses that attack critical organs, including the lungs and kidneys.
“We always seek to identify and develop potent and effective antibody therapeutics for the viral targets we are studying, but this effort has added complexity,” said Carnahan, VVC’s associate director, and professor of Pediatrics and Radiology & Radiological Sciences.
“Here we are tasked with identifying a single antibody combination that protects against all hantaviruses from all over the world, while completing that discovery program faster than ever,” he said.
Crowe, who directs the VVC, is the Ann Scott Carell Professor and a professor of Pediatrics and Pathology, Microbiology & Immunology at VUMC.
VUMC’s antibody collaboration with the DOD goes back to January 2018, when the medical center signed a five-year cooperative agreement with the U.S. Defense Advanced Research Projects Agency (DARPA) to develop protective treatments that can be rushed to health care providers within weeks after a viral outbreak — anywhere in the world.
By April, less than three months after their first sprint began, VVC researchers and colleagues in Boston, Seattle and St. Louis developed a protective antibody that potentially will prevent the spread of Zika. The mosquito-transmitted virus can cause severe birth defects in babies whose mothers were infected while pregnant.
In 2023, DARPA’s Pandemic Protection Platform (P3) program was transitioned to the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) and its Joint Project Lead for CBRND Enabling Technologies (JPL CBRND EB) as part of JPEO-CBRND’s Medical Countermeasures Platform Technologies (MCMPT) P3 program.
“Time is a critical component of defense,” David Bailey, acting director for Advanced Technology Platforms at JPL CBRND EB, said in a news release. “We can use that data to enable a capabilities-based response to the joint force when they need it.”
“The Hantavirus Sprint allows us to tackle a known threat on an existing platform and optimize to enable a faster and more robust response for future threats,” added Chris Spiridon, acting deputy director for Advanced Technology Platforms at JPL CBRND EB.
Hantaviruses are primarily transmitted by rodents, but they also may be spread through close human contact. Currently circulating in Eastern Europe, they can cause a severe upper respiratory disease with a fatality rate approaching 40%.
Last year, VVC researchers, with colleagues at the University of Oxford, described how, at the molecular level, a human monoclonal antibody isolated at VUMC prevents infection by a New World hantavirus called Sin Nombre. This work is an important step toward developing the first effective protection against the virus.
In June, VUMC launched a first-in-human clinical trial to determine the safety and efficacy of an experimental monoclonal antibody isolated by the VVC team against enterovirus D68 (EV-D68). The virus can cause severe respiratory disease and — in rare cases — a debilitating, polio-like neurologic condition.
VVC’s list of target viruses is extensive and growing. To meet the challenge, the research infrastructure at VUMC is expanding, with additional BSL3 (biosafety level 3) laboratories, and more than $100 million in new extramural support, Crowe said.
VVC’s facilities “arguably house the most capable infectious disease antibody discovery unit globally,” he said. “We are committed to advancing our work in developing monoclonal antibodies for even more viruses.”
