“Ultra-Potent” Antibody Against Multiple COVID-19 Variants Discovered

“Ultra-potent” antibody to COVID-19 variants isolated at Vanderbilt University Medical Center.

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

The antibody has rare properties that make it a valuable addition to the limited set of broadly reactive antibody therapeutic candidates, researchers reported in the journal Cell Reports.

The technology, called LIBRA-seq, has helped accelerate the discovery of antibodies that can neutralize SARS-CoV-2. It also allows researchers to screen for antibodies against other viruses that have not yet caused disease in humans, but have a high potential to do so.

Ivelin Georgiev, PhD, director of the Vanderbilt Program in Computational Microbiology and Immunology and associate director of the Vanderbilt Institute for Infection, Immunology and Inflammation. Credit: Vanderbilt University Medical Center

“This is a way to proactively build a repertoire of potential therapies” against future outbreaks, said Ivelin Georgiev, PhD, director of the Vanderbilt program in Computational Microbiology and Immunology and associate director of the Vanderbilt Institute for Infection, Immunology and Inflammation. .

“The pathogens continue to evolve, and we’re actually catching up,” said Georgiev, an associate professor of Pathology, Microbiology & Immunology, and Computer Science, and a 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 in the future,” he said.

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

The antibody has unusual genetic and structural features that set it apart from other monoclonal antibodies commonly used to treat COVID-19. The thinking is that SARS-CoV-2 is less likely to mutate to escape an antibody it hasn’t “seen” before.

LIBRA-seq stands for Linking B-cell Receptor to Antigen Specificity through sequencing. It was developed in 2019 by Ian Setliff, PhD, a former graduate student in Georgiev’s lab who now works in the biotechnology industry, and by Andrea Shiakolas, a current Vanderbilt graduate student.

Setliff wondered if he could map the genetic sequences of antibodies and the identity of specific viral antigens, the protein markers that antibodies recognize and attack, simultaneously and in a high-throughput manner. The goal was to find a faster way to identify antibodies that will target a specific viral antigen.

With the help of VUMC’s core laboratory for genomics, Vanderbilt Technologies for Advanced Genomics (VANTAGE), the Vanderbilt Flow Cytometry Shared Resource, and the Advanced Computing Center for Research and Education (ACCRE) at Vanderbilt University, Georgiev put Setliff’s idea to the test. posed. It worked.

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

“It would have been impossible three or four years ago to move at the speed we have now,” Georgiev said. “A lot has changed in a very short time when it comes to the discovery of monoclonal antibodies and the development of vaccines.”

There is no time to lose. “If we give the virus enough time,” he said, “so many other variants will emerge,” one or more of which — by dodging current vaccines — may be even worse than the delta variant.

“That’s exactly why you should have as many options as possible,” Georgiev said. The antibody described in this article “basically gives you another tool in the toolbox.”

Reference: “Potent Neutralization of SARS-CoV-2 Variants of Concern by an Antibody with an Unusual Genetic Signature and Structural Mode of Peak Recognition” by
Kevin J. Kramer, Nicole V. Johnson, Andrea R. Shiakolas, Naveenchandra Suryadevara, Sivakumar Periasamy, Nagarajan Raju, Jazmean K. Williams, Daniel Wrapp, Seth J. Zost, Lauren M. Walker, Steven C. Wall, Clinton M. Holt, Ching-Lin Hsieh, Rachel E. Sutton, Ariana Paulo, Edgar Davidson, Benjamin J. Doranz, James E. Crowe, Jr., Alexander Bukreyev, Robert H. Carnahan, Jason S. McLellan, Ivelin S. Georgiev, Accepted , Cell reports.
DOI: 10.116/j.celrep.2021.109784

Georgiev and Jason McLellan, PhD, at the University of Texas at Austin, are the corresponding authors of the paper. Kevin Kramer and Nicole Johnson, graduate students at VUMC and UT Austin respectively, are the first authors of the paper.

In addition to Shiakolas, other VUMC co-authors include Naveen Suryadevara, PhD, Nagarajan Raju, PhD, Seth Zost, PhD, Lauren Walker, Steven Wall, Clinton Holt, Rachel Sutton, Ariana Paulo, James Crowe, Jr., MD, and Robert Carnahan, PhD.

The research was supported in part by grants from the National Institutes of Health AI131722, AI157155, AI127521 and AI095202, the Hays Foundation COVID-19 Research Fund, the Dolly Parton COVID-19 Research Fund at Vanderbilt, Fast Grants, the Welch Foundation and the Mercatus Center of George Mason University.