Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display

Shiho Tanaka, C. Anders Olson, Christopher O. Barnes, Wendy Higashide, Marcos Gonzalez, Justin Taft, Ashley Richardson, Marta Martin-Fernandez, Dusan Bogunovic, Priyanthi N.P. Gnanapragasam, Pamela J. Bjorkman, Patricia Spilman, Kayvan Niazi, Shahrooz Rabizadeh, Patrick Soon-Shiong

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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.

Original languageEnglish
Article number110348
JournalCell Reports
Volume38
Issue number6
DOIs
StatePublished - 8 Feb 2022

Keywords

  • SARS-CoV-2
  • SARS-CoV-2 variants
  • anti-spike antibody
  • antibody
  • antibody design
  • mRNA display
  • neutralizing antibody

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