Taking a proactive approach

Posted by William Snyder on Wednesday, March 5, 2025 in Around the Medical Center, Spring 2025 .

Vanderbilt University Medical Center has joined an extraordinary national effort to develop and stockpile new vaccines and antibody therapies against a host of viral threats to prevent another pandemic.

Pending the availability of funds, the National Institute of Allergy and Infectious Diseases of the National Institutes of Health expects to commit approximately $100 million annually to the program, called ReVAMPP, (Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness), the NIH announced in 2024.

Developed in the wake of the COVID-19 pandemic, which killed millions of people worldwide and cost the United States economy trillions of dollars, ReVAMPP will support a coordinating center and seven research centers, including VUMC, with a focus on nine virus groups that pose the greatest risk.

VUMC’s three-year, $13 million per year grant (number U19AI181979) will enable researchers at the Vanderbilt Center for

Antibody Therapeutics (VCAT) to accelerate their investigations of bunyaviruses, which include life-threatening respiratory and hemorrhagic fever viruses, and picornaviruses, notably enterovirus D68.

They also will contribute to ReVAMPP projects led by the University of Texas Medical Branch in Galveston and Washington University School of Medicine in St. Louis targeting other viral threats, including mosquito-transmitted Eastern equine encephalitis.

“We have long stated that antibodies and vaccines for emerging infections should be generated and tested prior to large outbreaks, not after disaster has occurred,” said James Crowe Jr., MD, director of the VCAT, formerly known as the Vanderbilt Vaccine Center, and the grant’s principal investigator. “This new federal program gives us the support to prepare ahead of time for prevention and treatment of some of the most lethal infections that threaten to cause human epidemics.”

Like SARS-CoV-2, a member of the coronavirus family that causes COVID-19, hundreds of viruses known to cause disease in humans evolve rapidly, making it difficult to develop long-lasting methods to contain them.

To meet this challenge, ReVAMPP is focusing on “prototype pathogens,” representatives of each virus group. Researchers will look for “sites of vulnerability” in the prototypes that can inform development of antibody therapies and vaccines capable of blocking every group member.

Through its new Bunyavirus and Picornavirus Pandemic Pathogen Preparedness (BP4) Center, the VCAT will assemble a consortium of 20 leading investigators in picornavirus and bunyavirus virology, immunology, vaccine biology and antibody sciences from universities, research institutes and industry partners across the country.

Housed in a state-of-the-art lab atop a medical research tower on the Main Campus, the VCAT is uniquely prepared to contribute to ReVAMPP, said the center’s associate director, Robert Carnahan, PhD, professor of Pediatrics and of Radiology and Radiological Sciences.

VCAT researchers have developed techniques for rapidly isolating clones of white blood cells that make antibodies targeting viral proteins. Once identified, these “monoclonal” antibodies are refined into potential therapies that can latch onto and “neutralize” specific viruses.

The VCAT is perhaps best known for isolating in early 2020 — and in a record 25 days — monoclonal antibodies that neutralize the COVID-19 virus.

In late 2021, the Food and Drug Administration approved a long-acting combination of antibodies discovered at VUMC and developed by the global biopharmaceutical company AstraZeneca for emergency use to prevent COVID-19 in high-risk adults and children.

Five years earlier, VCAT researchers reported the isolation of monoclonal antibodies that were cross-reactive for the viruses that cause monkeypox (now called mpox), cowpox and smallpox.

The World Health Organization declared mpox a public health emergency of international concern. Crowe said his group is working with the federal government and industry to advance to clinical testing antibodies they had isolated in 2016.

“We already did the discovery work,” said Crowe, the Ann Scott Carell Professor and professor of Pediatrics and Pathology, Microbiology and Immunology. “They’re ready for clinical trials at the moment we need them, instead of starting from scratch.”

Earlier, VCAT researchers isolated neutralizing antibodies against enterovirus D68, which has been linked to a rare but devastating polio-like illness in children, acute flaccid myelitis. After further development and testing in partnership with two biotechnology companies, VUMC launched the first-in-human trial of one of the antibodies in June 2024.

Also in June 2024, the VCAT began a “sprint” sponsored by the U.S. Department of Defense to discover neutralizing antibodies against hantaviruses, for which there currently are no approved vaccines or treatments. Transmitted primarily by rodents, hantaviruses can cause severe upper respiratory disease with a fatality rate approaching 40%.

Long before COVID-19, Crowe and his colleagues were advocating for a broad-based, proactive program of antibody and vaccine discovery and development. ReVAMPP, he said, is a big step in the right direction.