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, the researchers reported in the journal Cell Reports.
This is a way to proactively build a repertoire of potential therapies” against future epidemics,
Ivelin Georgiev, PhD, director of the Vanderbilt Program in Computational Microbiology and Immunology
“Pathogens continue to evolve and we are trying to catch up quickly,” Georgiev says. “A more proactive approach is needed that anticipates future epidemics before they occur. To prevent the recurrence of viruses such as COVID-19, or even worse things in the future."
An ultra potent antibody
In the submitted report, Georgiev and his colleagues describe the isolation of a monoclonal antibody from a recovered COVID-19 patient that “shows potent neutralization” against SARS-CoV-2. It is also effective against virus variants that are slowing efforts to control the pandemic, including the Delta variant.
What makes this antibody “ultra potent”? The antibody has uncommon genetic and structural characteristics that distinguish it from other monoclonal antibodies commonly used to treat COVID-19. And the idea is that SARS-CoV-2 is much less likely to mutate to escape an antibody it has never “seen” before.
All thanks to LIBRA-seq
The technology used to isolate the ultra-potent antibody, called LIBRA-seq, will allow researchers to examine antibodies against other viruses, even those that haven't yet caused human disease but could.
LIBRA-seq stands for Linking B-cell Receptor to Antigen Specificity (linking the B cell receptor to an Antigen) 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 from Andrea Shiakolas, a current graduate student of Vanderbilt.
Setliff wondered whether LIBRA-seq could map the genetic sequences of antibodies and the identities 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 focused on a specific viral antigen. Georgiev put Setliff's idea to the test. And it worked.
The efforts led by Setliff and Shiakolas culminated in a manuscript describing the development of the LIBRA-seq technology proof of concept that was published in Cell magazine in 2019.
Now we proceed faster
“It would have been impossible three or four years ago to move at the speed we have now,” Georgiev says. “A lot has changed in a very short period of time when it comes to monoclonal antibody discovery and vaccine development.”
Thank goodness, because there's no time to waste. “If we give the virus time,” says the researcher, “so many other variants arise,” one or more of which (evading current vaccines) could be even worse than the Delta variant.
“It's exactly why you need to have as many options as possible,” Georgiev said. The ultra-potent antibody described in this paper “adds another important tool to our toolbox.”
Source: Vanderbilt University
