'Ultra-potent' antibody against SARS-CoV-2 variants isolated

Date:
September 22, 2021
Source:
Vanderbilt University Medical Center
Summary:
Researchers have discovered an 'ultra-potent' monoclonal antibody
against multiple variants of SARS-CoV-2, the virus responsible
for COVID-19, including the delta variant.



FULL STORY ==========================================================================
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 characteristics 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 speed up the discovery of antibodies that can neutralize SARS-CoV-2. It also enables researchers
to screen antibodies against other viruses that have not yet caused
human disease but which have a high potential of doing so.

"This is one way to proactively build a repertoire of potential
therapeutics" 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 keep evolving, and we're basically playing catch-up," said Georgiev, 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
occur is needed to prevent a repeat of COVID-19, "or something worse
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 also is effective
against variants of the virus that are slowing efforts to control the
pandemic.

The antibody has uncommon genetic and structural characteristics that distinguish it from other monoclonal antibodies commonly used to treat
COVID- 19. The thought is that SARS-CoV-2 will be 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 identities of specific viral antigens, the proteins markers that antibodies recognize and attack, simultaneously and in a high-throughput
way. The goal was to find a faster way of identifying antibodies that
will hone in on a specific viral antigen.

With the help of VUMC's core genomics laboratory, Vanderbilt Technologies
for Advanced Genomics (VANTAGE), the Vanderbilt Flow Cytometry Shared
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 led by Setliff and Shiakolas culminated in a manuscript
describing proof-of-concept development of the LIBRA-seq technology that
was published in the journalCell in 2019.

"It would have been impossible three or four years ago to move at the
speed that we are right now," Georgiev said. "A lot has changed in a very
short period of time when it comes to monoclonal antibody discovery as
well as vaccine development." There is no time to lose. "If we give
the virus enough time," he said, "there will so many other variants
that arise," one or more of which -- by evading current vaccines --
may be even worse than the delta variant.

"That's exactly why you need to have as many options as possible,"
Georgiev said. The antibody described in this paper "basically gives
you another tool in the toolbox." Georgiev and Jason McLellan, PhD,
at the University of Texas at Austin, are the paper's corresponding
authors. Kevin Kramer and Nicole Johnson, graduate students at VUMC and
UT Austin, respectively, are the paper's first authors.

In addition to Shiakolas, other VUMC coauthors are 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 National Institutes of Health grants 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.

========================================================================== Story Source: Materials provided by
Vanderbilt_University_Medical_Center. Note: Content may be edited for
style and length.


========================================================================== Journal Reference:
1. 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, Alexander Bukreyev,
Robert H.

Carnahan, Jason S. McLellan, Ivelin S. Georgiev. Potent
neutralization of SARS-CoV-2 variants of concern by an
antibody with an uncommon genetic signature and structural
mode of spike recognition. Cell Reports, 2021; 109784 DOI:
10.1016/j.celrep.2021.109784 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210922121911.htm

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