tetano
Editor, Senior Moderator
Cell
. 2022 May 20;S0092-8674(22)00598-0.
doi: 10.1016/j.cell.2022.05.014. Online ahead of print.
Potent cross-reactive antibodies following Omicron breakthrough in vaccinees
Rungtiwa Nutalai[SUP] 1 [/SUP], Daming Zhou[SUP] 2 [/SUP], Aekkachai Tuekprakhon[SUP] 1 [/SUP], Helen M Ginn[SUP] 3 [/SUP], Piyada Supasa[SUP] 1 [/SUP], Chang Liu[SUP] 4 [/SUP], Jiandong Huo[SUP] 5 [/SUP], Alexander J Mentzer[SUP] 6 [/SUP], Helen M E Duyvesteyn[SUP] 5 [/SUP], Aiste Dijokaite-Guraliuc[SUP] 1 [/SUP], Donal Skelly[SUP] 7 [/SUP], Thomas G Ritter[SUP] 8 [/SUP], Ali Amini[SUP] 9 [/SUP], Sagida Bibi[SUP] 10 [/SUP], Sandra Adele[SUP] 8 [/SUP], Sile Ann Johnson[SUP] 8 [/SUP], Bede Constantinides[SUP] 11 [/SUP], Hermione Webster[SUP] 11 [/SUP], Nigel Temperton[SUP] 12 [/SUP], Paul Klenerman[SUP] 13 [/SUP], Eleanor Barnes[SUP] 13 [/SUP], Susanna J Dunachie[SUP] 14 [/SUP], Derrick Crook[SUP] 11 [/SUP], Andrew J Pollard[SUP] 15 [/SUP], Teresa Lambe[SUP] 16 [/SUP], Philip Goulder[SUP] 17 [/SUP], OPTIC consortium, ISARIC4C consortium; Neil G Paterson[SUP] 3 [/SUP], Mark A Williams[SUP] 3 [/SUP], David R Hall[SUP] 3 [/SUP], Juthathip Mongkolsapaya[SUP] 4 [/SUP], Elizabeth E Fry[SUP] 5 [/SUP], Wanwisa Dejnirattisai[SUP] 18 [/SUP], Jingshan Ren[SUP] 19 [/SUP], David I Stuart[SUP] 20 [/SUP], Gavin R Screaton[SUP] 21 [/SUP]
Affiliations
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.
Keywords: BA.1; BA.1.1; BA.2; COVID-19; Omicron; SARS-CoV-2; antibody responses; crystallography; immune escape; neutralization; receptor binding domain; variants of concern.
. 2022 May 20;S0092-8674(22)00598-0.
doi: 10.1016/j.cell.2022.05.014. Online ahead of print.
Potent cross-reactive antibodies following Omicron breakthrough in vaccinees
Rungtiwa Nutalai[SUP] 1 [/SUP], Daming Zhou[SUP] 2 [/SUP], Aekkachai Tuekprakhon[SUP] 1 [/SUP], Helen M Ginn[SUP] 3 [/SUP], Piyada Supasa[SUP] 1 [/SUP], Chang Liu[SUP] 4 [/SUP], Jiandong Huo[SUP] 5 [/SUP], Alexander J Mentzer[SUP] 6 [/SUP], Helen M E Duyvesteyn[SUP] 5 [/SUP], Aiste Dijokaite-Guraliuc[SUP] 1 [/SUP], Donal Skelly[SUP] 7 [/SUP], Thomas G Ritter[SUP] 8 [/SUP], Ali Amini[SUP] 9 [/SUP], Sagida Bibi[SUP] 10 [/SUP], Sandra Adele[SUP] 8 [/SUP], Sile Ann Johnson[SUP] 8 [/SUP], Bede Constantinides[SUP] 11 [/SUP], Hermione Webster[SUP] 11 [/SUP], Nigel Temperton[SUP] 12 [/SUP], Paul Klenerman[SUP] 13 [/SUP], Eleanor Barnes[SUP] 13 [/SUP], Susanna J Dunachie[SUP] 14 [/SUP], Derrick Crook[SUP] 11 [/SUP], Andrew J Pollard[SUP] 15 [/SUP], Teresa Lambe[SUP] 16 [/SUP], Philip Goulder[SUP] 17 [/SUP], OPTIC consortium, ISARIC4C consortium; Neil G Paterson[SUP] 3 [/SUP], Mark A Williams[SUP] 3 [/SUP], David R Hall[SUP] 3 [/SUP], Juthathip Mongkolsapaya[SUP] 4 [/SUP], Elizabeth E Fry[SUP] 5 [/SUP], Wanwisa Dejnirattisai[SUP] 18 [/SUP], Jingshan Ren[SUP] 19 [/SUP], David I Stuart[SUP] 20 [/SUP], Gavin R Screaton[SUP] 21 [/SUP]
Affiliations
- PMID: 35662412
- DOI: 10.1016/j.cell.2022.05.014
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.
Keywords: BA.1; BA.1.1; BA.2; COVID-19; Omicron; SARS-CoV-2; antibody responses; crystallography; immune escape; neutralization; receptor binding domain; variants of concern.