tetano
Editor, Senior Moderator
Nat Struct Mol Biol
. 2021 May 12.
doi: 10.1038/s41594-021-00596-4. Online ahead of print.
Structural basis for broad coronavirus neutralization
Maximilian M Sauer[SUP] 1 [/SUP], M Alejandra Tortorici[SUP] 1 2 [/SUP], Young-Jun Park[SUP] 1 [/SUP], Alexandra C Walls[SUP] 1 [/SUP], Leah Homad[SUP] 3 [/SUP], Oliver J Acton[SUP] 1 [/SUP], John E Bowen[SUP] 1 [/SUP], Chunyan Wang[SUP] 4 [/SUP], Xiaoli Xiong[SUP] 1 5 [/SUP], Willem de van der Schueren[SUP] 6 7 [/SUP], Joel Quispe[SUP] 1 [/SUP], Benjamin G Hoffstrom[SUP] 8 [/SUP], Berend-Jan Bosch[SUP] 4 [/SUP], Andrew T McGuire[SUP] 9 10 11 [/SUP], David Veesler[SUP] 12 [/SUP]
Affiliations
Abstract
Three highly pathogenic ?-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight ?-coronavirus spike glycoproteins, including all five human-infecting ?-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with ?-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-?-coronavirus vaccine.
. 2021 May 12.
doi: 10.1038/s41594-021-00596-4. Online ahead of print.
Structural basis for broad coronavirus neutralization
Maximilian M Sauer[SUP] 1 [/SUP], M Alejandra Tortorici[SUP] 1 2 [/SUP], Young-Jun Park[SUP] 1 [/SUP], Alexandra C Walls[SUP] 1 [/SUP], Leah Homad[SUP] 3 [/SUP], Oliver J Acton[SUP] 1 [/SUP], John E Bowen[SUP] 1 [/SUP], Chunyan Wang[SUP] 4 [/SUP], Xiaoli Xiong[SUP] 1 5 [/SUP], Willem de van der Schueren[SUP] 6 7 [/SUP], Joel Quispe[SUP] 1 [/SUP], Benjamin G Hoffstrom[SUP] 8 [/SUP], Berend-Jan Bosch[SUP] 4 [/SUP], Andrew T McGuire[SUP] 9 10 11 [/SUP], David Veesler[SUP] 12 [/SUP]
Affiliations
- PMID: 33981021
- DOI: 10.1038/s41594-021-00596-4
Abstract
Three highly pathogenic ?-coronaviruses have crossed the animal-to-human species barrier in the past two decades: SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight ?-coronavirus spike glycoproteins, including all five human-infecting ?-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with ?-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-?-coronavirus vaccine.