“Ultra-potent” antibody against COVID-19 variants

Technology developed at Vanderbilt University Medical Center has led to the discovery of an “ultra-potent” monoclonal antibody against several variants of SARS-CoV-2, the virus responsible for COVID-19, including the delta variant.

The antibody has rare characteristics that make it a valuable addition to the limited set of widely reactive antibody therapy candidates, researchers reported in the journal Sept. 15. Cell reports.

The technology, called LIBRA-seq, has accelerated the discovery of antibodies capable of neutralizing SARS-CoV-2. It also allows researchers to screen for antibodies against other viruses that have not yet caused human disease but have high potential to do so.

“It’s a way to proactively build a repository of potential therapies” against future outbreaks, said Ivelin Georgiev, Ph.D., director of the Vanderbilt program in computational microbiology and immunology and associate director of the Vanderbilt Institute for Infection, Immunology and Inflammation.

“Pathogens continue to evolve and we are essentially catching up,” said Georgiev, associate professor of pathology, microbiology and immunology and member of the Vanderbilt Vaccine Center.

A more proactive approach that anticipates future outbreaks before they happen is needed to prevent a recurrence of COVID-19, “or something worse from happening in the future,” he said.

In their report, Georgiev and his colleagues describe the isolation of a monoclonal antibody from a patient who had recovered from COVID-19 that “shows potent neutralization” against SARS-CoV-2. It is also effective against variants of the virus that are slowing efforts to control the pandemic.

The antibody exhibits unusual genetic and structural characteristics that distinguish it from other monoclonal antibodies commonly used to treat COVID-19. The idea is that SARS-CoV-2 will be less likely to mutate to escape an antibody it has not “seen” before.

LIBRA-seq stands for Linking B-cell Receptor to Antigen Specificity through sequencing. It was developed in 2019 by Ian Setliff, Ph.D., a former graduate student of Georgiev’s lab now working in the biotech industry, and Andrea Shiakolas, currently a graduate student at Vanderbilt.

Setliff wondered if he could map the genetic sequences of antibodies and the identities of specific viral antigens, the protein markers that antibodies recognize and attack, simultaneously and at high throughput. The goal was to find a faster way to identify antibodies that would focus on a specific viral antigen.

With assistance from VUMC’s Basic Genomics Lab, Vanderbilt Technologies for Advanced Genomics (VANTAGE), Vanderbilt’s Shared Flow Cytometry Resource, and Vanderbilt University’s Advanced Computing Center for Research and Education (ACCRE) , Georgiev put Setliff’s idea to the test. It worked.

The efforts of Setliff and Shiakolas resulted in a manuscript describing the development of the proof of concept of LIBRA-seq technology which was published in the journal Cell in 2019.

“It would have been impossible three or four years ago to move forward at the speed we know today,” said Georgiev. “A lot has changed in a very short time with regard to the discovery of monoclonal antibodies as well as the development of vaccines.”

There’s no time to lose. “If we give the virus enough time,” he said, “there will be so many other variants that will appear,” one or more of which – avoiding current vaccines – could be even worse than the delta variant. .

“This is exactly why you need to have as many options as possible,” Georgiev said. The antibody described in this article “essentially gives you another tool in the toolbox.”