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Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display.
Tanaka, Shiho; Olson, C Anders; Barnes, Christopher O; Higashide, Wendy; Gonzalez, Marcos; Taft, Justin; Richardson, Ashley; Martin-Fernandez, Marta; Bogunovic, Dusan; Gnanapragasam, Priyanthi N P; Bjorkman, Pamela J; Spilman, Patricia; Niazi, Kayvan; Rabizadeh, Shahrooz; Soon-Shiong, Patrick.
  • Tanaka S; ImmunityBio, Inc., 9920 Jefferson Boulevard, Culver City, CA 90232, USA.
  • Olson CA; ImmunityBio, Inc., 9920 Jefferson Boulevard, Culver City, CA 90232, USA. Electronic address: anders.olson@immunitybio.com.
  • Barnes CO; Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
  • Higashide W; ImmunityBio, Inc., 9920 Jefferson Boulevard, Culver City, CA 90232, USA.
  • Gonzalez M; ImmunityBio, Inc., 9920 Jefferson Boulevard, Culver City, CA 90232, USA.
  • Taft J; Center for Inborn Errors of Immunity, Icahn School of Medicine at Mount Sinai, 1 Gustave Lane, Levy Plaza, New York, NY 10029-5674, USA; Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave Lane, Levy Plaza, New York, NY 10029-5674, USA; Department of Mi
  • Richardson A; Center for Inborn Errors of Immunity, Icahn School of Medicine at Mount Sinai, 1 Gustave Lane, Levy Plaza, New York, NY 10029-5674, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, 1 Gustave Lane, Levy Plaza, New York, NY 10029-5674, USA; Precision Immunology Institute, Icahn
  • Martin-Fernandez M; Center for Inborn Errors of Immunity, Icahn School of Medicine at Mount Sinai, 1 Gustave Lane, Levy Plaza, New York, NY 10029-5674, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, 1 Gustave Lane, Levy Plaza, New York, NY 10029-5674, USA; Precision Immunology Institute, Icahn
  • Bogunovic D; Center for Inborn Errors of Immunity, Icahn School of Medicine at Mount Sinai, 1 Gustave Lane, Levy Plaza, New York, NY 10029-5674, USA; Department of Pediatrics, Icahn School of Medicine at Mount Sinai, 1 Gustave Lane, Levy Plaza, New York, NY 10029-5674, USA; Precision Immunology Institute, Icahn
  • Gnanapragasam PNP; Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
  • Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.
  • Spilman P; ImmunityBio, Inc., 9920 Jefferson Boulevard, Culver City, CA 90232, USA.
  • Niazi K; ImmunityBio, Inc., 9920 Jefferson Boulevard, Culver City, CA 90232, USA.
  • Rabizadeh S; ImmunityBio, Inc., 9920 Jefferson Boulevard, Culver City, CA 90232, USA.
  • Soon-Shiong P; ImmunityBio, Inc., 9920 Jefferson Boulevard, Culver City, CA 90232, USA. Electronic address: patrick@nantworks.com.
Cell Rep ; 38(6): 110348, 2022 02 08.
Article in English | MEDLINE | ID: covidwho-1712500
ABSTRACT
The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identify a set of antibodies against SARS-CoV-2 spike (S) proteins and characterize the structures of nAbs that recognize epitopes in the S1 subunit of the S glycoprotein. These structural studies reveal distinct binding modes for several antibodies, including the targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interact with angiotensin-converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1. Further, we engineer a potent ACE2-blocking nAb to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants. We demonstrate that mRNA display is an approach for the rapid identification of nAbs that can be used in combination to combat emerging SARS-CoV-2 variants.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Diagnostic study / Risk factors Topics: Variants Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.110348

Full text: Available Collection: International databases Database: MEDLINE Type of study: Diagnostic study / Risk factors Topics: Variants Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.110348