December 2, 2021

Long-acting antibody combo developed at VUMC reduces COVID-19 risk and symptoms

The global biopharmaceutical company AstraZeneca announced more good news about its long-acting combination of two monoclonal antibodies against COVID-19 that were discovered at Vanderbilt University Medical Center.

In a prevention trial, one prophylactic, intramuscular injection of the antibody combination, called AZD7442, reduced the risk of symptoms occurring after exposure to the COVID-19 virus by 83%, even in people with medical conditions that impaired their immune response to infection.

In already-infected patients who had symptoms of mild-to-moderate COVID-19 for three days or less, an intramuscular injection of AZD7442 reduced the risk of severe illness or death by 88% compared to inactive placebo, the company reported.

These results have not yet been published in a peer-reviewed scientific journal, and the U.S. Food and Drug Administration is considering AstraZeneca’s request that AZD7442 be granted Emergency Use Authorization to be given to patients.

But according to James Crowe Jr., MD, director of the Vanderbilt Vaccine Center who led the antibody discovery team at VUMC, the latest news gives further credence to the role that monoclonal antibodies may play in controlling COVID-19 and other viral infections with pandemic potential.

“I believe monoclonal antibodies will probably be the principal tool we use for emerging infections,” he said on Nov. 18 during an online Global COVID Lab Meeting hosted by the New York-based Human Vaccines Project. “They will be complementary and sometimes more important than vaccines.”

Crowe is the Ann Scott Carell Professor and professor of Pediatrics and Pathology, Microbiology & Immunology at VUMC.

Vaccines provide “active” immunity by stimulating the body to produce infection-fighting antibodies. But an estimated 5 million people in the United States with serious illnesses like cancer or who have received organ transplants are significantly immunocompromised and may not be able to respond effectively to vaccination, Crowe said.

The findings reported by AstraZeneca suggest that they can be protected instead by “passive” immunization, the injection of laboratory-made antibodies.

“You can give this preventative treatment to virtually any individual,” Crowe said. “It could be a 100-year-old person, a stem-cell transplant recipient who has no immune system—it doesn’t matter the health condition. That’s not true of active vaccination.”

There also is evidence that monoclonal antibodies in some cases may be more effective and provide longer-lasting protection than vaccination, even in the general population. “At some point, antibodies will be comparable in terms of efficacy and duration,” he said. “I believe we’re seeing that right now.”

Crowe described advances in technologies that enable the rapid development of monoclonal antibodies:

  • Automated, high-throughput techniques for generating tens of thousands of monoclonal antibodies from single, antibody-producing B cells.
  • Structural biology techniques that, by revealing how antibodies bind to their viral targets, speed the selection of the most broadly effective ones.
  • Next-generation sequencing that has led to the creation, from synthetic genomes, of never-before-seen antibodies against specific viruses.

Thanks to these technologies, researchers have been able to generate monoclonal antibodies against a host of disease-causing viruses in a matter of weeks.

But while a speedy response to pandemics like COVID-19 is essential, Crowe and his colleagues around the country have gone further and are developing antibody products against viruses that have not yet emerged as important human pathogens.

Through the Advanced Human Epidemic Antibody Defenses initiative, AHEAD100, they are making — and stockpiling — human monoclonal antibodies for the 100 most likely causes of future epidemics.

In the prevention and treatment of infectious diseases, Crowe said, “antibodies increasingly are the future.”