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

Cell reports (2022-02-04)
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

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.

Product Number
Product Description

Insulin solution human, sterile-filtered, BioXtra, suitable for cell culture
Hemocyanin from Megathura crenulata (keyhole limpet), PBS solution
KOD Hot Start DNA Polymerase, High fidelity DNA polymerase designed for accurate PCR amplification of long strand and GC- rich DNA templates for cloning and cDNA amplification applications.
IgG from human serum, reagent grade, ≥95% (SDS-PAGE), essentially salt-free, lyophilized powder