EMD-14887
OMI-2 FAB IN COMPLEX WITH SARS-COV-2 BETA SPIKE GLYCOPROTEIN
EMD-14887
Single-particle4.0 Å
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Map released: 01/06/2022
Last modified: 20/11/2024
Sample Organism:
Homo sapiens,
Severe acute respiratory syndrome coronavirus 2,
Enterobacteria phage T4
Sample: OMI-2 FAB IN COMPLEX WITH SARS-COV-2 BETA SPIKE GLYCOPROTEIN
Fitted models: 7zr9 (Avg. Q-score: 0.259)
Deposition Authors: Duyvesteyn HME, Ren J, Stuart DI
Sample: OMI-2 FAB IN COMPLEX WITH SARS-COV-2 BETA SPIKE GLYCOPROTEIN
Fitted models: 7zr9 (Avg. Q-score: 0.259)
Deposition Authors: Duyvesteyn HME, Ren J, Stuart DI
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Potent cross-reactive antibodies following Omicron breakthrough in vaccinees.
Nutalai R
,
Zhou D
,
Tuekprakhon A
,
Ginn HM,
Supasa P,
Liu C,
Huo J,
Mentzer AJ,
Duyvesteyn HME,
Dijokaite-Guraliuc A
,
Skelly D
,
Ritter TG
,
Amini A
,
Bibi S,
Adele S,
Johnson SA,
Constantinides B,
Webster H,
Temperton N
,
Klenerman P,
Barnes E
,
Dunachie SJ
,
Crook D,
Pollard AJ,
Lambe T,
Goulder P,
Paterson NG,
Williams MA
,
Hall DR,
Mongkolsapaya J
,
Fry EE,
Dejnirattisai W,
Ren J,
Stuart DI
,
Screaton GR
(2022) Cell , 185 , 2116 - 2131.e18
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(2022) Cell , 185 , 2116 - 2131.e18
Abstract:
Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1, and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site; however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and-function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focused in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains, and many show broad reactivity with variants of concern.
Highly transmissible Omicron variants of SARS-CoV-2 currently dominate globally. Here, we compare neutralization of Omicron BA.1, BA.1.1, and BA.2. BA.2 RBD has slightly higher ACE2 affinity than BA.1 and slightly reduced neutralization by vaccine serum, possibly associated with its increased transmissibility. Neutralization differences between sub-lineages for mAbs (including therapeutics) mostly arise from variation in residues bordering the ACE2 binding site; however, more distant mutations S371F (BA.2) and R346K (BA.1.1) markedly reduce neutralization by therapeutic antibody Vir-S309. In-depth structure-and-function analyses of 27 potent RBD-binding mAbs isolated from vaccinated volunteers following breakthrough Omicron-BA.1 infection reveals that they are focused in two main clusters within the RBD, with potent right-shoulder antibodies showing increased prevalence. Selection and somatic maturation have optimized antibody potency in less-mutated epitopes and recovered potency in highly mutated epitopes. All 27 mAbs potently neutralize early pandemic strains, and many show broad reactivity with variants of concern.