Scientists from Vanderbilt University and Vanderbilt University Medical Center are teaming with colleagues across the country to develop a vaccine that protects against all alphaviruses, including chikungunya and the often-lethal Eastern equine encephalitis virus (EEEV).
The project, part of a major initiative launched this fall by the Advanced Research Projects Agency for Health (ARPA-H) of the U.S. Department of Health and Human Services, aims to design computational “tool kits” that can speed development of multi-virus vaccines targeting some of the greatest infectious threats to human health.
Under the initiative, called Antigens Predicted for Broad Viral Efficacy through Computational Experimentation, or APECx, ARPA-H has committed up to $204 million to support four separate research efforts. Vanderbilt University will receive up to $46 million over five years for its alphavirus project.
Jens Meiler, PhD, Distinguished Research Professor of Chemistry at Vanderbilt, is the project’s principal investigator. He and his colleagues will apply advanced technology, including computational modeling, artificial intelligence-driven predictions, and structural biology approaches to develop a multi-alphavirus vaccine providing broad coverage and long-lasting protection.
James Crowe Jr., MD, Ann Scott Carell Professor and University Distinguished Professor of Pediatrics and Chemistry, leads the VUMC team. He and C. Buddy Creech, MD, MPH, Edie Carell Johnson Professor of Pediatrics, will contribute their expertise in virology, immunology and clinical trials.
Crowe and colleagues in the Vanderbilt Vaccine Center 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 — with laser-like focus — can latch onto and neutralize specific viruses.
Creech, who directs the Vanderbilt Vaccine Research Program, recently has led clinical trials to determine the safety and efficacy of avian (bird) flu vaccines, Moderna’s COVID-19 vaccine, and a monoclonal antibody targeting enterovirus D68, which causes respiratory illness and, rarely, a debilitating, polio-like neurologic condition in children.
Transmitted largely by mosquitoes, alphaviruses are a diverse family of viruses that cause neurological (encephalitic) and musculoskeletal (arthritogenic) diseases in humans, and for which there are no approved vaccines or treatments.
Chikungunya, which causes fever and severe, debilitating joint and muscle pain, infects millions of people in tropical regions every year.
EEEV, which infects the central nervous system of humans, horses and other animals, has a fatality rate exceeding 30%. This summer, health officials advised people in several Massachusetts towns to stay indoors at night after an 80-year-old man in the area contracted the disease.
In 2021, researchers at VUMC and Washington University School of Medicine in St. Louis isolated monoclonal antibodies that prevented alphavirus infection in laboratory and animal studies. That year, a German-based drug company began a Phase 1 clinical trial of a monoclonal antibody against chikungunya that had been identified at VUMC.
APECx takes the research a step further.
“This project integrates expertise across multiple disciplines, including artificial intelligence, basic virology, preclinical vaccine development, industry engagement and clinical trial design,” Creech said.
It will use innovative techniques to design immunogens (antigens) that can trigger strong and long-lasting immune responses against entire families of pathogenic viruses. The aim is to develop next-generation vaccines to protect against future outbreaks — and pandemics.
Key contributors to Vanderbilt’s alphavirus project are Cristina Martina, PhD, research assistant professor of Chemistry, Kevin Schey, PhD, Stevenson Professor and professor of Biochemistry, and Carie Fortenberry, program manager.
Collaborators and their institutions are:
- Hamilton Bennett, MS, MBA, Moderna;
- Michael Diamond, MD, PhD, Washington University School of Medicine;
- Gaurav Giaha, MD, DPhil, Harvard Medical School;
- Torben Schiffner, PhD, Darrell Irvine, PhD, Andrew Ward, PhD, and Ian Wilson, PhD, Scripps Research;
- William Klimstra, PhD, University of Pittsburgh;
- Mark Slifka, PhD, Oregon Health & Science University; and
- Daniela Weiskopf, PhD, La Jolla Institute for Immunology.
Three other APECx projects for antigen and vaccine development will target herpesviruses, including cytomegalovirus and herpes simplex virus, and flaviviruses, which include the West Nile, dengue, and Zika viruses.
In a news release announcing the program, ARPA-H Director Renee Wegrzyn, PhD, said, “ARPA-H is investing in groundbreaking tools for vaccine design on a scale that has not been possible before. We aim to revolutionize vaccine development and accessibility in the U.S. and around the globe by harnessing these machine learning tools to prevent today’s viral infections and get ahead of tomorrow’s.”
