VUMC Scientists Race to Find Anti-Zika Antibodies

Scientists at Vanderbilt University Medical Center and colleagues in Boston, Seattle and St. Louis are racing to develop - in a mere 90 days - a protective antibody-based treatment that can stop the spread of the Zika virus.

This is the first of four “scientific sprints” sponsored by the Defense Advanced Research Agency (DARPA), part of the U.S. Department of Defense, under a five-year cooperative agreement worth up to $28 million that was signed last year.

The program, formally known as the Pandemic Protection Platform (P3), aims to prepare and deploy protective antibody-based treatments against viral outbreaks that threaten public health and security around the globe, said the program’s research director Robert Carnahan, PhD, associate professor of Pediatrics in the Vanderbilt University School of Medicine.

The program’s principal investigator, James Crowe Jr., MD, directs the Vanderbilt Vaccine Center and is the Ann Scott Carell Professor in the Departments of Pediatrics and of Pathology, Microbiology and Immunology.

Crowe and his colleagues have developed monoclonal antibodies that will be tested in clinical trials for their ability to protect against Zika. The virus can cause severe birth defects in babies whose mothers were infected when they were pregnant.

It can take months to years, however, to develop therapeutic antibodies using conventional methods. Antibody treatments also must be given intravenously, which is difficult to provide urgently to hundreds of people in remote areas.

Instead, the researchers are trying a new, audacious tactic: isolating the nucleic acid, the messenger RNA, which encodes the antibody protein, and delivering it through a quick, intramuscular injection. Any cell that takes up the RNA will begin to produce the desired antibody almost immediately.

Crowe said the work requires seamless coordination of multidisciplinary groups working in perfect synchronization, in a system designed by Carnahan and implemented by a team of project managers led by Merissa Mayo, PMP (project management professional).

The pipeline incorporates rapid discovery work by immunologists, protein engineering and virology experts led by Pavlo Gilchuk, PhD, molecular biologists and genetics experts led by Robin Bombardi, MS, bioinformatics and computer scientists led by Cinque Soto, PhD, associate professor of Pediatrics, and administrative oversight led by Megan Leksell.

But time is short. The Zika project began on Jan. 14 and must be completed by April 14. This is where VUMC’s partners come in.

Anti-viral antibodies discovered at VUMC go to researchers at Washington University in St. Louis led by Michael Diamond, MD, PhD, and Galit Alter, PhD, and colleagues at the Ragon Institute of MGH, MIT and Harvard in Boston. They “down-select” to identify antibodies with the most potent anti-viral activity.

Genetic sequences for the lead antibodies are sent to a team at the Infectious Disease Research Institute (IDRI) in Seattle led by Steve Reed, PhD and Neal Van Hoeven, PhD. They produce and optimize the RNA-encoded delivery product.

Follow-up in-vivo evaluations of the RNA-delivered antibodies are conducted at Washington University and at Beth Israel Deaconess Medical Center in Boston.

The researchers will reconvene next year for a second “sprint” to develop an antibody therapy that can stop the spread of another nasty virus, such as chikungunya, but this time more rapidly - in just 60 days. Another 60-day sprint will be launched in early 2021.

To meet these deadlines, researchers may need to work weekends. “Yes, we want quality,” Carnahan said. “Yes, we want potent antibodies. But none of that matters if we can’t deliver in a timely (manner) …Viruses do not have work weeks. The clock continues to count.”

Carnahan credited Crowe for the program’s success to date. “He has a deep appreciation that it’s not just the science that wins,” Carnahan said. “You have to have a well-run ship.”
 
Source: Vanderbilt University Medical Center