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Racing against time: Rapid, high-throughput discovery of antibody therapeutics for SARS-CoV-2 – Science Magazine

July 9th, 2020 6:43 pm

Since the World Health Organization declared it a pandemic in March 2020, the novel coronavirus SARS-CoV-2 has caused millions of infections and hundreds of thousands of deaths worldwide. Currently there is no cure, and many initial treatments being tested against COVID-19 were designed for other viral infections. Multiple drugmakers are scrambling to find treatments that might help fight off the coronavirus or prevent infections altogetherin a Herculean effort to collapse the typical 1015-year drug development timeline to under a year.

Antiviral human monoclonal antibodies (mAbs) are promising drug candidates for preventing or treating severe viral diseases, but the long timelineson the order of yearsneeded for antibody discovery, functional analysis, preclinical studies, and manufacturing limit their rapid deployment and use as immunotherapeutics. Vanderbilt University Medical Center researchers Robert Carnahan and Pavlo Gilchuk are part of the scientific team attempting to compress the timeline for potent antiviral antibody discovery and characterization by integrating a series of advances in single-cell messenger RNA sequence analysis, bioinformatics, synthetic biology, and high-throughput functional analysis. Their work enabled the rapid discovery of a diverse panel of highly potent antiviral human mAbs against the SARS-CoV-2 Spike protein and the validation of their activity both in vitro and in vivo. These results provide a potential framework for expedited antibody discovery programs against viral pathogens of global concern.

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Vanderbilt Vaccine CenterNashville, TN

Dr. Pavlo Gilchuk received his M.S. in biochemistry and his doctorate in biotechnology from Taras Shevchenko National University of Kyiv, Ukraine. His work there was largely focused on single-chain antibody design and discovery. From 2002 to 2009, he was employed by Phage Biotechnology Corporation in San Diego, California, where he advanced from engineer biologist to research group manager. Dr. Gilchuk also held the position of staff scientist at the Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine (Kyiv), and served as laboratory head at the State Institute of Genetic and Regenerative Medicine, Academy of Medical Sciences of Ukraine (Kyiv). Upon transitioning to the Vanderbilt University Medical Center in Nashville, Tennessee, his initial research was directed to large-scale vaccinia virusderived T cell epitope discovery, elucidation of immunological features of lung-resident memory CD8+ T cells, and development of platforms for T celltargeted mucosal vaccination. Dr. Gilchuk is now a senior staff scientist in the laboratory of James E. Crowe, Jr. at the Vanderbilt Vaccine Center (VVC) and leads antibody-discovery technology development and evolution within this large academic team. In addition, he is currently working on methods development for rapid identification of therapeutic antibodies against viral diseases (the Defense Advanced Research Projects Agency [DARPA] Pandemic Prevention Platform program).

Vanderbilt Vaccine CenterNashville, TN

Dr. Robert Carnahan is associate director of the Vanderbilt Vaccine Center at Vanderbilt University Medical Center and an associate professor in pediatrics and radiology. He has a high level of experience with monoclonal antibodies and antibody engineering. He directed the Vanderbilt Antibody and Protein Resource (VAPR) for over 10 years. The facility grew to the point of conducting an average of 150 antibody projects per year, comprising more than 70 unique Vanderbilt investigators as well as several academic and industry partners from across the country (e.g., the University of California, Los Angeles; the Fred Hutchinson Cancer Research Center; Purdue University; Kolltan Pharmaceuticals; Becton Dickinson). Both academic and industry projects focused increasingly on therapeutic targets (cancer, viral pathogens, autoimmunity, diabetes, etc.), with work in the lab ranging from discovery to preclinical activities. Dr. Carnahan has brought this focus on innovation applied to antibody generation and detailed characterization to the Crowe Lab and the Vanderbilt Vaccine Center. During this time, he has also held numerous regional and national leadership roles within the Association of Biomolecular Resource Facilities (ABRF), to develop advances in methodologies and technical standards, oversee collaborative studies, and implement training opportunities for lab directors and personnel. Furthermore, he is also a national leader in the design and implementation of Lean management systems for biological laboratories.

Science/AAASWashington, D.C.

Dr. Oberst did her undergraduate training at the University of Maryland, College Park, and her Ph.D. in Tumor Biology at Georgetown University, Washington D.C. She combined her interests in science and writing by pursuing an M.A. in Journalism from the Philip Merrill College of Journalism at the University of Maryland, College Park. Dr. Oberst joined Science/AAAS in 2016 as the Assistant Editor for Custom Publishing. Before then she worked at Nature magazine, the Howard Hughes Medical Institute, The Endocrine Society, and the National Institutes of Mental Health.

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Racing against time: Rapid, high-throughput discovery of antibody therapeutics for SARS-CoV-2 - Science Magazine

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