“Ultra-potent” antibody versus COVID-19 versions separated at Vanderbilt University Medical Center
An innovation established at Vanderbilt University Medical Center has resulted in the discovery of an “ultra-potent” monoclonal antibody versus several variants of SARS-CoV-2, the infection responsible for COVID-19, consisting of the delta variation.
The antibody has uncommon characteristics that make it an important addition to the restricted set of broadly reactive antibody therapeutic candidates, scientists reported in the journal Cell Reports.
The innovation, called LIBRA-seq, has helped speed up the discovery of antibodies that can reduce the effects of SARS-CoV-2. It likewise makes it possible for researchers to screen antibodies versus other infections that have actually not yet caused human illness however which have a high capacity of doing so.
Ivelin Georgiev, PhD, director of the Vanderbilt Program in Computational Microbiology and Immunology and associate director of the Vanderbilt Institute for Immunology, infection and swelling. Credit: Vanderbilt University Medical Center.
” This is one way to proactively develop a repertoire of possible therapies” against future break outs, said Ivelin Georgiev, PhD, director of the Vanderbilt Program in Computational Microbiology and Immunology and associate director of the Vanderbilt Institute for Inflammation, immunology and infection.
” The pathogens keep progressing, and were generally playing catch-up,” said Georgiev, associate teacher of Pathology, Microbiology & & Immunology and Computer Science, and a member of the Vanderbilt Vaccine Center.
A more proactive approach that expects future outbreaks before they take place is required to prevent a repeat of COVID-19, “or something even worse taking place in the future,” he said.
In their report, Georgiev and his coworkers explain the isolation of a monoclonal antibody from a patient who had actually recovered from COVID-19 that “shows powerful neutralization” against SARS-CoV-2. It likewise works versus versions of the infection that are slowing efforts to control the pandemic.
The antibody has unusual hereditary and structural qualities that differentiate it from other monoclonal antibodies frequently used to deal with COVID-19. The idea is that SARS-CoV-2 will be less likely to alter to get away an antibody it hasnt “seen” before.
LIBRA-seq stands for Linking B-cell Receptor to Antigen Specificity through sequencing. It was established in 2019 by Ian Setliff, PhD, a previous college student in Georgievs lab who now operates in the biotechnology industry, and by Andrea Shiakolas, a current Vanderbilt graduate trainee.
Setliff wondered if he might map the hereditary sequences of antibodies and the identities of particular viral antigens, the proteins markers that antibodies attack and acknowledge, all at once and in a high-throughput method. The objective was to discover a faster way of determining antibodies that will focus on a particular viral antigen.
With the aid of VUMCs core genomics lab, Vanderbilt Technologies for Advanced Genomics (VANTAGE), the Vanderbilt Flow Cytometry Shared Resource, and Vanderbilt Universitys Advanced Computing Center for Research and Education (ACCRE), Georgiev put Setliffs 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 journal Cell in 2019.
” It would have been difficult 3 or four years ago to move at the speed that we are right now,” Georgiev stated. “A lot has altered in an extremely short amount of time when it pertains to monoclonal antibody discovery as well as vaccine development.”
There is no time to lose. “If we give the virus adequate time,” he stated, “there will many other versions that occur,” one or more of which– by evading existing vaccines– may be even worse than the delta variant.
” Thats precisely why you need to have as numerous options as possible,” Georgiev stated. The antibody described in this paper “generally provides you another tool in the toolbox.”
Referral: “Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an unusual genetic signature and structural mode of spike recognition” byKevin 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: 10.1016/ j.celrep.2021.109784.
Georgiev and Jason McLellan, PhD, at the University of Texas at Austin, are the papers corresponding authors. Kevin Kramer and Nicole Johnson, college students at VUMC and UT Austin, respectively, are the papers very 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, AI127521, ai095202 and ai157155, 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.