Vanderbilt Health researchers call for pandemic prevention

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By: Bill Snyder

The next pandemic may arrive in the United States via cruise ship or commercial flight originating halfway around the world.

It also may be homegrown, arising from a lethal, easily transmissible variant of a respiratory virus like avian influenza for which there are no approved treatments or vaccines to save lives or limit its contagion.

This is what keeps Vanderbilt Health’s virus hunters awake at night: not knowing when the next “bad actor” will emerge but dreading with a fair degree of certainty that someday, somehow, it will.

“There are 10 to 12 scary viruses (infecting) animals and people every day, all over the world,” said James Crowe Jr., MD, whose team is known internationally for isolating antibodies that can neutralize dangerous viruses. “Some of these are knocking on the door.”

Another pandemic is not inevitable, Crowe said. But preventing it will take money. And so far, the American people have been ambivalent about making such an investment.

“I’m calling on us as citizens,” he said. “Who do we want to be?”

Crowe, Director of the Vanderbilt Center for Antibody Therapeutics, and Associate Director Robert Carnahan, PhD, oversee one of the world’s largest antiviral antibody research and development efforts in academia or industry, with about 40 scientists and staff.

During the past three decades, monoclonal antibodies against five dangerous viruses that were isolated and characterized by center researchers have been evaluated for safety and efficacy in humans. One of them, Evusheld (COVID-19), was licensed for clinical use.

Antibodies against four more viruses are on the path to clinical trials in the next two years, and several others are in preclinical development.

In early May, passengers on a cruise ship sailing from Argentina fell ill with hantavirus, which is spread by mice and rats. Three people died, and some of the American passengers were flown to the National Quarantine Unit in Omaha, Nebraska, to be monitored for symptoms.

“We have hantavirus antibodies,” said Carnahan, Professor of Pediatrics, “but they haven’t been manufactured for human use. They could have been … The people who are in quarantine in Nebraska right now could have gotten the antibody. They could have been safe and protected.”

The same goes for the continuing outbreak of the Bundibugyo Ebola virus in the Democratic Republic of Congo and in neighboring Uganda, where since early May close to 1,000 infections and more than 200 deaths have been reported.

“We had excellent antibodies (against Bundibugyo) about 10 years ago,” said Crowe, the Ann Scott Carell Professor and University Distinguished Professor of Pediatrics. The antibodies were licensed to a biotech firm, but so far, he said, lack of money has held up further development.

For the past several years, Crowe and Carnahan have been lobbying for what they call AHEAD100, an Advanced Human Epidemic Antibody Defenses initiative that would make, test and stockpile human monoclonal antibodies against the 100 viruses most likely to cause future epidemics.

The Vanderbilt Center for Antibody Therapeutics has received large-scale government grants and contracts to fund the discovery of human antiviral antibodies. The problem is the next step — finding corporate partners to develop the antibodies through human testing.

That step currently costs $40 million for each antibody. To do a Phase 1 clinical trial on all 100 viruses with epidemic potential would cost $4 billion.

“Four billion dollars sounds like a lot of money,” Crowe said. “But every time one of these outbreaks occurs, we spend far more than that on the economic and social disruption that occurs with no treatments to offer people, and people die.”

In 2023, a team of economists and other experts at the University of Southern California estimated that the economic toll of the COVID-19 pandemic, which killed more than a million Americans, would reach $14 trillion dollars.

Yet finding partners has been difficult. Most biotechnology and pharmaceutical companies have left the infectious disease business, focusing instead on drugs that treat chronic diseases, like cancer, and which generate a more reliable return on investment.

It’s easy to blame industry and the government for the yawning gap between antibody discovery and clinical application. But “we elect the government,” Crowe said. “They’re doing what we want.” Similarly, biotech and pharma companies have a fiduciary responsibility to their stockholders, who include millions of retirees.

If the public supported the investment needed to prevent another pandemic, industry and the government would follow suit. But, Crowe added, “it really has to be a groundswell of people saying, ‘We’re tired of being reactive … We want to be ready.’”