Structures of Omicron spike complexes and implications for neutralizing antibody development

A cocktail containing two synergetic antibodies broadly neutralizes SARS-CoV-2 and its variants including Omicron BA.1 and BA.2

“…The expression and purification procedures for the SARS-CoV-2 Omicron S protein were described previously 39 . In brief, the gene encoding stabilized Omicron S ECD HexaPro was constructed and expressed using FreeStyle 293-F cells.…”

“…To build the structures of the Omicron S-55A8 Fab complex, the structure of the Omicron S-510A5 complex model (PDB ID: 7WS5) 39 was placed and rigid-body fitted into cryo-EM electron density maps using UCSF Chimera 47 . The 55A8 Fab model was first predicted using Phyre2 48 and then manually built in Coot 0.9 49 with the guidance of the cryo-EM electron density maps, and overall real-space refinements were performed using Phenix 1.19 50 .…”

Broadly Neutralizing Antibodies to SARS-CoV-2 Provide Novel Insights Into the Neutralization of Variants and Other Human Coronaviruses

“…Among these, only Sotrovimab (S309) neutralizes Omicron (BA.1) variant but poorly neutralizes the BA.2 variant ( Cao et al., 2022 ). Other therapeutic nAbs have been ineffective towards Omicron, mainly due to the presence of extensive mutations in their epitopes, remodeling of the antigenic surface of the spike trimer and dominance of RBD closed state of Omicron spike protein ( Figure 1C ) ( Cao et al., 2022 ; Gobeil et al., 2022 ; Guo et al., 2022 ; Zhang et al., 2022 ). Therefore, for the treatment of Omicron infected patients, US-FDA has provided emergency use authorization (EUA) to a class III or RBD-5 targeting bnAb Bebtelovimab (or LyCoV1404) in Feb 2022 that maintains its potency and neutralizes all SARS-CoV-2 VOCs ( Westendorf et al., 2022 ).…”

SARS-CoV-2 infection in a stem cell transplant recipient grafted from a SARS-CoV-2-positive donor

“…Some studies reported that HSCT recipients with COVID-19 disease have a poor outcome, but they were carried out during the period 2020-2021, when the predominant variants were Alpha and Delta [ 1 , 2 , 5 ]. Although the mutations identified in the Omicron spike protein (about 37) have led to serious concerns over antibody responses [ 6 , 7 ], it seems that most T-cell immune responses are retained, potentially underpinning protection from a severe disease [ 6 , 8 , 9 ]. A recent study on vaccinated subjects evidenced a significant decrease in memory B cells and neutralizing antibodies at 6 months, with up to 42% less for the Omicron variant than others, whilst, there was an >80% average functional preservation of T-cell responses [ 8 ].…”