tetano
Editor, Senior Moderator
Cell Rep
. 2022 Jan 20;110348.
doi: 10.1016/j.celrep.2022.110348. Online ahead of print.
Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display
Shiho Tanaka[SUP] 1 [/SUP], C Anders Olson[SUP] 2 [/SUP], Christopher O Barnes[SUP] 3 [/SUP], Wendy Higashide[SUP] 1 [/SUP], Marcos Gonzalez[SUP] 1 [/SUP], Justin Taft[SUP] 4 [/SUP], Ashley Richardson[SUP] 5 [/SUP], Marta Martin-Fernandez[SUP] 5 [/SUP], Dusan Bogunovic[SUP] 5 [/SUP], Priyanthi N P Gnanapragasam[SUP] 3 [/SUP], Pamela J Bjorkman[SUP] 3 [/SUP], Patricia Spilman[SUP] 1 [/SUP], Kayvan Niazi[SUP] 1 [/SUP], Shahrooz Rabizadeh[SUP] 1 [/SUP], Patrick Soon-Shiong[SUP] 6 [/SUP]
Affiliations
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: SARS-CoV-2; SARS-CoV-2 variants; anti-spike antibody; antibody; antibody design; mRNA display; neutralizing antibody.
. 2022 Jan 20;110348.
doi: 10.1016/j.celrep.2022.110348. Online ahead of print.
Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display
Shiho Tanaka[SUP] 1 [/SUP], C Anders Olson[SUP] 2 [/SUP], Christopher O Barnes[SUP] 3 [/SUP], Wendy Higashide[SUP] 1 [/SUP], Marcos Gonzalez[SUP] 1 [/SUP], Justin Taft[SUP] 4 [/SUP], Ashley Richardson[SUP] 5 [/SUP], Marta Martin-Fernandez[SUP] 5 [/SUP], Dusan Bogunovic[SUP] 5 [/SUP], Priyanthi N P Gnanapragasam[SUP] 3 [/SUP], Pamela J Bjorkman[SUP] 3 [/SUP], Patricia Spilman[SUP] 1 [/SUP], Kayvan Niazi[SUP] 1 [/SUP], Shahrooz Rabizadeh[SUP] 1 [/SUP], Patrick Soon-Shiong[SUP] 6 [/SUP]
Affiliations
- PMID: 35114110
- DOI: 10.1016/j.celrep.2022.110348
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: SARS-CoV-2; SARS-CoV-2 variants; anti-spike antibody; antibody; antibody design; mRNA display; neutralizing antibody.