tetano
Editor, Senior Moderator
Cell
. 2021 Mar 30;S0092-8674(21)00428-1.
doi: 10.1016/j.cell.2021.03.055. Online ahead of print.
Antibody evasion by the P.1 strain of SARS-CoV-2
Wanwisa Dejnirattisai[SUP] 1 [/SUP], Daming Zhou[SUP] 2 [/SUP], Piyada Supasa[SUP] 3 [/SUP], Chang Liu[SUP] 4 [/SUP], Alexander J Mentzer[SUP] 5 [/SUP], Helen M Ginn[SUP] 6 [/SUP], Yuguang Zhao[SUP] 2 [/SUP], Helen M E Duyvesteyn[SUP] 2 [/SUP], Aekkachai Tuekprakhon[SUP] 3 [/SUP], Rungtiwa Nutalai[SUP] 3 [/SUP], Beibei Wang[SUP] 3 [/SUP], C?sar L?pez-Camacho[SUP] 3 [/SUP], Jose Slon-Campos[SUP] 3 [/SUP], Thomas S Walter[SUP] 2 [/SUP], Donal Skelly[SUP] 7 [/SUP], Sue Ann Costa Clemens[SUP] 8 [/SUP], Felipe Gomes Naveca[SUP] 9 [/SUP], Valdinete Nascimento[SUP] 9 [/SUP], Fernanda Nascimento[SUP] 9 [/SUP], Cristiano Fernandes da Costa[SUP] 10 [/SUP], Paola Cristina Resende[SUP] 11 [/SUP], Alex Pauvolid-Correa[SUP] 12 [/SUP], Marilda M Siqueira[SUP] 11 [/SUP], Christina Dold[SUP] 13 [/SUP], Robert Levin[SUP] 14 [/SUP], Tao Dong[SUP] 15 [/SUP], Andrew J Pollard[SUP] 13 [/SUP], Julian C Knight[SUP] 16 [/SUP], Derrick Crook[SUP] 17 [/SUP], Teresa Lambe[SUP] 18 [/SUP], Elizabeth Clutterbuck[SUP] 13 [/SUP], Sagida Bibi[SUP] 13 [/SUP], Amy Flaxman[SUP] 18 [/SUP], Mustapha Bittaye[SUP] 18 [/SUP], Sandra Belij-Rammerstorfer[SUP] 18 [/SUP], Sarah C Gilbert[SUP] 18 [/SUP], Miles W Carroll[SUP] 19 [/SUP], Paul Klenerman[SUP] 20 [/SUP], Eleanor Barnes[SUP] 20 [/SUP], Susanna J Dunachie[SUP] 21 [/SUP], Neil G Paterson[SUP] 6 [/SUP], Mark A Williams[SUP] 6 [/SUP], David R Hall[SUP] 6 [/SUP], Ruben J G Hulswit[SUP] 2 [/SUP], Thomas A Bowden[SUP] 2 [/SUP], Elizabeth E Fry[SUP] 2 [/SUP], Juthathip Mongkolsapaya[SUP] 22 [/SUP], Jingshan Ren[SUP] 23 [/SUP], David I Stuart[SUP] 24 [/SUP], Gavin R Screaton[SUP] 25 [/SUP]
Affiliations
Abstract
Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.
Keywords: P.1; RBD; SARS-CoV-2; VH3-53; antibody; escape; neutralization; spike; structure; variant.
. 2021 Mar 30;S0092-8674(21)00428-1.
doi: 10.1016/j.cell.2021.03.055. Online ahead of print.
Antibody evasion by the P.1 strain of SARS-CoV-2
Wanwisa Dejnirattisai[SUP] 1 [/SUP], Daming Zhou[SUP] 2 [/SUP], Piyada Supasa[SUP] 3 [/SUP], Chang Liu[SUP] 4 [/SUP], Alexander J Mentzer[SUP] 5 [/SUP], Helen M Ginn[SUP] 6 [/SUP], Yuguang Zhao[SUP] 2 [/SUP], Helen M E Duyvesteyn[SUP] 2 [/SUP], Aekkachai Tuekprakhon[SUP] 3 [/SUP], Rungtiwa Nutalai[SUP] 3 [/SUP], Beibei Wang[SUP] 3 [/SUP], C?sar L?pez-Camacho[SUP] 3 [/SUP], Jose Slon-Campos[SUP] 3 [/SUP], Thomas S Walter[SUP] 2 [/SUP], Donal Skelly[SUP] 7 [/SUP], Sue Ann Costa Clemens[SUP] 8 [/SUP], Felipe Gomes Naveca[SUP] 9 [/SUP], Valdinete Nascimento[SUP] 9 [/SUP], Fernanda Nascimento[SUP] 9 [/SUP], Cristiano Fernandes da Costa[SUP] 10 [/SUP], Paola Cristina Resende[SUP] 11 [/SUP], Alex Pauvolid-Correa[SUP] 12 [/SUP], Marilda M Siqueira[SUP] 11 [/SUP], Christina Dold[SUP] 13 [/SUP], Robert Levin[SUP] 14 [/SUP], Tao Dong[SUP] 15 [/SUP], Andrew J Pollard[SUP] 13 [/SUP], Julian C Knight[SUP] 16 [/SUP], Derrick Crook[SUP] 17 [/SUP], Teresa Lambe[SUP] 18 [/SUP], Elizabeth Clutterbuck[SUP] 13 [/SUP], Sagida Bibi[SUP] 13 [/SUP], Amy Flaxman[SUP] 18 [/SUP], Mustapha Bittaye[SUP] 18 [/SUP], Sandra Belij-Rammerstorfer[SUP] 18 [/SUP], Sarah C Gilbert[SUP] 18 [/SUP], Miles W Carroll[SUP] 19 [/SUP], Paul Klenerman[SUP] 20 [/SUP], Eleanor Barnes[SUP] 20 [/SUP], Susanna J Dunachie[SUP] 21 [/SUP], Neil G Paterson[SUP] 6 [/SUP], Mark A Williams[SUP] 6 [/SUP], David R Hall[SUP] 6 [/SUP], Ruben J G Hulswit[SUP] 2 [/SUP], Thomas A Bowden[SUP] 2 [/SUP], Elizabeth E Fry[SUP] 2 [/SUP], Juthathip Mongkolsapaya[SUP] 22 [/SUP], Jingshan Ren[SUP] 23 [/SUP], David I Stuart[SUP] 24 [/SUP], Gavin R Screaton[SUP] 25 [/SUP]
Affiliations
- PMID: 33852911
- PMCID: PMC8008340
- DOI: 10.1016/j.cell.2021.03.055
Abstract
Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding site mutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.
Keywords: P.1; RBD; SARS-CoV-2; VH3-53; antibody; escape; neutralization; spike; structure; variant.