Native-like SARS-CoV-2 Spike Glycoprotein Expressed by ChAdOx1 nCoV-19/AZD1222 Vaccine

Watanabe, Yasunori; Mendonça, L.G.D.; Allen, Elizabeth; Howe, Andrew; Lee, Mercede; Allen, Joel D.; Chawla, Himanshi; Pulido, David; Donnellan, Francesca R.; Davies, H. Dele; Ulaszewska, Marta; Belij‐Rammerstorfer, Sandra; Morris, Susan; Krebs, Anna-Sophia; Dejnirattisai, Wanwisa; Mongkolsapaya, Juthathip; Supasa, Piyada; Screaton, Gavin; Green, Catherine; Lambe, Teresa; Zhang, Peijun; Gilbert, Sarah C.; Crispin, Max

doi:10.1021/acscentsci.1c00080

Cited by 144 publications

(107 citation statements)

References 53 publications

Supporting

Mentioning

100

Contrasting

Unclassified

Order By: Relevance

“…Subsequent studies have investigated the presentation of N-linked glycans on S protein produced for vaccination, notably the Novavax full length S protein and S protein isolated following administration of the ChAdOx-nCoV-19 vector. 39 , 40 The observed glycan signatures were broadly in agreement with previous analyses. However, these studies involved the truncation of glycan structures using glycosidase treatment, which is useful for categorizing glycans into high-mannose or complex-type glycans and determining the potential N-glycosylation site (PNGS) occupancy on small amounts of material but does not allow for the identification of changes in terminal glycan processing such as sialylation.…”

supporting

confidence: 90%

Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation

et al. 2021

Self Cite

View full text Add to dashboard Cite

A central tenet in the design of vaccines is the display of native-like antigens in the elicitation of protective immunity. The abundance of N-linked glycans across the SARS-CoV-2 spike protein is a potential source of heterogeneity among the many different vaccine candidates under investigation. Here, we investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against S protein from infectious virus, cultured in Vero cells. We find patterns that are conserved across all samples, and this can be associated with site-specific stalling of glycan maturation that acts as a highly sensitive reporter of protein structure. Molecular dynamics simulations of a fully glycosylated spike support a model of steric restrictions that shape enzymatic processing of the glycans. These results suggest that recombinant spike-based SARS-CoV-2 immunogen glycosylation reproducibly recapitulates signatures of viral glycosylation.

show abstract

supporting

confidence: 90%

Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Many experimental results on the spikes and their activation, bonding, and inactivation assisted in vaccine development [17,18,19]. The pharmaceutical and the vaccine industry would benefit from such detailed visualizations of internal structures and bonding, rate of unbonding, and the role of interventions [20,21,22,23].…”

Section: Introductionmentioning

confidence: 99%

Mathematical Analysis and Topology of SARS-CoV-2, Bonding with Cells and Unbonding

Rao

Krantz

2021

Preprint

View full text Add to dashboard Cite

We consider the structure of the novel coronavirus (SARS-Cov-2) in terms of the number of spikes that are critical in bonding with the cells in the host. Bonding formation is considered for selection criteria with and without any treatments. Functional mappings from the discrete space of spikes and cells and their analysis are performed. We found that careful mathematical constructions help in understanding the treatment impacts, and the role of vaccines within a host. Smale's famous 2-D horseshoe examples inspired us to create 3-D visualizations and understand the topological diffusion of spikes from one human organ to another organ. The pharma industry will benefit from such an analysis for designing efficient treatment and vaccine strategies.

show abstract

“…4 The majority of vaccines developed against SARS-CoV-2 use the S protein (e.g. genetically encoded via either mRNA/DNA cargo [5][6][7] or displayed on a nanoparticle surface 8 ) to elicit an immune response. Understanding how exactly antibodies (Abs) interact with the SARS-CoV-2 S protein is a crucial component for both continuing vaccine development as well as the rational design of target biotherapeutics (e.g.…”

Section: Introductionmentioning

confidence: 99%

Probing Affinity, Avidity, Anti-Cooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses

Yin

Lai

Caniels

et al. 2021

Preprint

View full text Add to dashboard Cite

Determining how antibodies interact with the spike (S) protein of the SARS-CoV-2 virus is critical for combating COVID-19. Structural studies typically employ simplified, truncated constructs that may not fully recapitulate the behaviour of the original complexes. Here, we combine two single particle mass analysis techniques (mass photometry and charge-detection mass spectrometry) to enable measurement of full IgG binding to the trimeric SARS-CoV-2 S ectodomain. Our experiments reveal that antibodies targeting the S-trimer typically prefer stoichiometries lower than the symmetry-predicted 3:1 binding. We determine that this behaviour arises from the interplay of steric clashes and avidity effects that are not reflected in common antibody constructs (i.e. Fabs). Surprisingly, these sub-stoichiometric complexes are fully effective at blocking ACE2 binding despite containing free receptor binding sites. Our results highlight the importance of studying antibody/antigen interactions using complete, multimeric constructs and showcase the utility of single particle mass analyses in unraveling these complex interactions.

show abstract

Native-like SARS-CoV-2 Spike Glycoprotein Expressed by ChAdOx1 nCoV-19/AZD1222 Vaccine

Cited by 144 publications

References 53 publications

Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation

Site-Specific Steric Control of SARS-CoV-2 Spike Glycosylation

Mathematical Analysis and Topology of SARS-CoV-2, Bonding with Cells and Unbonding

Probing Affinity, Avidity, Anti-Cooperativity, and Competition in Antibody and Receptor Binding to the SARS-CoV-2 Spike by Single Particle Mass Analyses

Contact Info

Product

Resources

About