scholarly journals SAS: A Platform of Spike Antigenicity for SARS-CoV-2

2021 ◽  
Vol 9 ◽  
Author(s):  
Lu Zhang ◽  
Ruifang Cao ◽  
Tiantian Mao ◽  
Yuan Wang ◽  
Daqing Lv ◽  
...  
Keyword(s):  
South Africa ◽  
Monoclonal Antibodies ◽  
Reference Strain ◽  
Experimental Tests ◽  
Vaccine Effectiveness ◽  
Experimental Results ◽  
Spike Protein ◽  
Binding Assays ◽  
Current Version ◽  
Antigenic Sites

Since the outbreak of SARS-CoV-2, antigenicity concerns continue to linger with emerging mutants. As recent variants have shown decreased reactivity to previously determined monoclonal antibodies (mAbs) or sera, monitoring the antigenicity change of circulating mutants is urgently needed for vaccine effectiveness. Currently, antigenic comparison is mainly carried out by immuno-binding assays. Yet, an online predicting system is highly desirable to complement the targeted experimental tests from the perspective of time and cost. Here, we provided a platform of SAS (Spike protein Antigenicity for SARS-CoV-2), enabling predicting the resistant effect of emerging variants and the dynamic coverage of SARS-CoV-2 antibodies among circulating strains. When being compared to experimental results, SAS prediction obtained the consistency of 100% on 8 mAb-binding tests with detailed epitope covering mutational sites, and 80.3% on 223 anti-serum tests. Moreover, on the latest South Africa escaping strain (B.1.351), SAS predicted a significant resistance to reference strain at multiple mutated epitopes, agreeing well with the vaccine evaluation results. SAS enables auto-updating from GISAID, and the current version collects 867K GISAID strains, 15.4K unique spike (S) variants, and 28 validated and predicted epitope regions that include 339 antigenic sites. Together with the targeted immune-binding experiments, SAS may be helpful to reduce the experimental searching space, indicate the emergence and expansion of antigenic variants, and suggest the dynamic coverage of representative mAbs/vaccines among the latest circulating strains. SAS can be accessed at https://www.biosino.org/sas.

scholarly journals SARS-CoV-2 variants resist antibody neutralization and broaden host ACE2 usage

2021 ◽  
Author(s):  
Ruoke Wang ◽  
Qi Zhang ◽  
Jiwan Ge ◽  
Wenlin Ren ◽  
Rui Zhang ◽  
...  
Keyword(s):  
South Africa ◽  
Monoclonal Antibodies ◽  
Molecular Basis ◽  
Spike Protein ◽  
Receptor Binding Domain ◽  
Antibody Neutralization ◽  
Vaccine Protection ◽  
Antigenic Sites ◽  
Global Pandemic ◽  
Crystal Structural

AbstractNew SARS-CoV-2 variants continue to emerge from the current global pandemic, some of which can replicate faster and with greater transmissibility and pathogenicity. In particular, UK501Y.V1 identified in UK, SA501Y.V2 in South Africa, and BR501Y.V3 in Brazil are raising serious concerns as they spread quickly and contain spike protein mutations that may facilitate escape from current antibody therapies and vaccine protection. Here, we constructed a panel of 28 SARS-CoV-2 pseudoviruses bearing single or combined mutations found in the spike protein of these three variants, as well as additional nine mutations that within or close by the major antigenic sites in the spike protein identified in the GISAID database. These pseudoviruses were tested against a panel of monoclonal antibodies (mAbs), including some approved for emergency use to treat SARS-CoV-2 infection, and convalescent patient plasma collected early in the pandemic. SA501Y.V2 pseudovirus was the most resistant, in magnitude and breadth, against mAbs and convalescent plasma, followed by BR501Y.V3, and then UK501Y.V1. This resistance hierarchy corresponds with Y144del and 242-244del mutations in the N-terminal domain as well as K417N/T, E484K and N501Y mutations in the receptor binding domain (RBD). Crystal structural analysis of RBD carrying triple K417N-E484K-N501Y mutations found in SA501Y.V2 bound with mAb P2C-1F11 revealed a molecular basis for antibody neutralization and escape. SA501Y.V2 and BR501Y.V3 also acquired substantial ability to use mouse and mink ACE2 for entry. Taken together, our results clearly demonstrate major antigenic shifts and potentially broadening the host range of SA501Y.V2 and BR501Y.V3, which pose serious challenges to our current antibody therapies and vaccine protection.

scholarly journals An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies

2021 ◽  
Author(s):  
Laura A VanBlargan ◽  
John M Errico ◽  
Peter Halfmann ◽  
Seth J Zost ◽  
James E. Crowe ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Severe Acute Respiratory Syndrome ◽  
Clinical Development ◽  
Spike Protein ◽  
Clinical Use ◽  
Receptor Binding Domain ◽  
Antigenic Sites ◽  
Recent Emergence ◽  
Therapeutic Monoclonal Antibodies ◽  
The Impact

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic resulting in millions of deaths worldwide. Despite the development and deployment of highly effective antibody and vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike protein jeopardize their efficacy. Indeed, the recent emergence of the highly-transmissible B.1.1.529 Omicron variant is especially concerning because of the number of mutations, deletions, and insertions in the spike protein. Here, using a panel of anti-receptor binding domain (RBD) monoclonal antibodies (mAbs) corresponding to those with emergency use authorization (EUA) or in advanced clinical development by Vir Biotechnology (S309, the parent mAbs of VIR-7381), AstraZeneca (COV2-2196 and COV2-2130, the parent mAbs of AZD8895 and AZD1061), Regeneron (REGN10933 and REGN10987), Lilly (LY-CoV555 and LY-CoV016), and Celltrion (CT-P59), we report the impact on neutralization of a prevailing, infectious B.1.1.529 Omicron isolate compared to a historical WA1/2020 D614G strain. Several highly neutralizing mAbs (LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59) completely lost inhibitory activity against B.1.1.529 virus in both Vero-TMPRSS2 and Vero-hACE2-TMPRSS2 cells, whereas others were reduced (~12-fold decrease, COV2-2196 and COV2-2130 combination) or minimally affected (S309). Our results suggest that several, but not all, of the antibody products in clinical use will lose efficacy against the B.1.1.529 Omicron variant and related strains.

Yaw Galloping of a TLWP Platform Under High Speed Currents by Analytical Methods and its Comparison With Experimental Results

2017 ◽  
Author(s):  
Francisco Lamas ◽  
Miguel A. M. Ramirez ◽  
Antonio Carlos Fernandes
Keyword(s):  
High Speed ◽  
Production Systems ◽  
Experimental Tests ◽  
Experimental Results ◽  
Analytical Methodology ◽  
New Approach ◽  
Laboratory Facilities ◽  
Polynomial Curve ◽  
Computational Fluid Dynamics Cfd ◽  
Cfd Analyses

Flow Induced Motions are always an important subject during both design and operational phases of an offshore platform life. These motions could significantly affect the performance of the platform, including its mooring and oil production systems. These kind of analyses are performed using basically two different approaches: experimental tests with reduced models and, more recently, with Computational Fluid Dynamics (CFD) dynamic analysis. The main objective of this work is to present a new approach, based on an analytical methodology using static CFD analyses to estimate the response on yaw motions of a Tension Leg Wellhead Platform on one of the several types of motions that can be classified as flow-induced motions, known as galloping. The first step is to review the equations that govern the yaw motions of an ocean platform when subjected to currents from different angles of attack. The yaw moment coefficients will be obtained using CFD steady-state analysis, on which the yaw moments will be calculated for several angles of attack, placed around the central angle where the analysis is being carried out. Having the force coefficients plotted against the angle values, we can adjust a polynomial curve around each analysis point in order to evaluate the amplitude of the yaw motion using a limit cycle approach. Other properties of the system which are flow-dependent, such as damping and added mass, will also be estimated using CFD. The last part of this work consists in comparing the analytical results with experimental results obtained at the LOC/COPPE-UFRJ laboratory facilities.

scholarly journals The Impact on Infectivity and Neutralization Efficiency of SARS-CoV-2 Lineage B.1.351 Pseudovirus

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 633
Author(s):  
Yeong Jun Kim ◽  
Ui Soon Jang ◽  
Sandrine M. Soh ◽  
Joo-Youn Lee ◽  
Hye-Ra Lee
Keyword(s):  
South Africa ◽  
Monoclonal Antibodies ◽  
Cell Fusion ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Receptor Binding Domain ◽  
Viral Spread ◽  
New Variant ◽  
Global Concern ◽  
The Impact

A new variant of SARS-CoV-2 B.1.351 lineage (first found in South Africa) has been raising global concern due to its harboring of multiple mutations in the spike that potentially increase transmissibility and yield resistance to neutralizing antibodies. We here tested infectivity and neutralization efficiency of SARS-CoV-2 spike pseudoviruses bearing particular mutations of the receptor-binding domain (RBD) derived either from the Wuhan strains (referred to as D614G or with other sites) or the B.1.351 lineage (referred to as N501Y, K417N, and E484K). The three different pseudoviruses B.1.351 lineage related significantly increased infectivity compared with other mutants that indicated Wuhan strains. Interestingly, K417N and E484K mutations dramatically enhanced cell–cell fusion than N501Y even though their infectivity were similar, suggesting that K417N and E484K mutations harboring SARS-CoV-2 variant might be more transmissible than N501Y mutation containing SARS-CoV-2 variant. We also investigated the efficacy of two different monoclonal antibodies, Casirivimab and Imdevimab that neutralized SARS-CoV-2, against several kinds of pseudoviruses which indicated Wuhan or B.1.351 lineage. Remarkably, Imdevimab effectively neutralized B.1.351 lineage pseudoviruses containing N501Y, K417N, and E484K mutations, while Casirivimab partially affected them. Overall, our results underscore the importance of B.1.351 lineage SARS-CoV-2 in the viral spread and its implication for antibody efficacy.

scholarly journals Rapid isolation and profiling of a diverse panel of human monoclonal antibodies targeting the SARS-CoV-2 spike protein

2020 ◽  
Vol 26 (9) ◽  
pp. 1422-1427 ◽  
Author(s):  
Seth J. Zost ◽  
Pavlo Gilchuk ◽  
Rita E. Chen ◽  
James Brett Case ◽  
Joseph X. Reidy ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Spike Protein ◽  
Human Monoclonal Antibodies ◽  
Rapid Isolation

scholarly journals Influenza Epidemiology and Vaccine Effectiveness among Patients with Influenza-Like Illness, Viral Watch Sentinel Sites, South Africa, 2005–2009

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e94681 ◽  
Author(s):  
Genevie M. Ntshoe ◽  
Johanna M. McAnerney ◽  
Stefano Tempia ◽  
Lucille Blumberg ◽  
Jocelyn Moyes ◽  
...  
Keyword(s):  
South Africa ◽  
Vaccine Effectiveness ◽  
Influenza Like Illness

scholarly journals Numerical and experimental evaluation of masonry prisms by finite element method

2017 ◽  
Vol 10 (2) ◽  
pp. 477-508 ◽  
Author(s):  
C. F.R. SANTOS ◽  
R. C. S. S. ALVARENGA ◽  
J. C. L. RIBEIRO ◽  
L. O CASTRO ◽  
R. M. SILVA ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Finite Element Method ◽  
High Strength Concrete ◽  
Numerical Models ◽  
High Strength ◽  
Experimental Tests ◽  
Experimental Results ◽  
Concrete Blocks ◽  
Micro Modeling ◽  
Modeling Strategy

Abstract This work developed experimental tests and numerical models able to represent the mechanical behavior of prisms made of ordinary and high strength concrete blocks. Experimental tests of prisms were performed and a detailed micro-modeling strategy was adopted for numerical analysis. In this modeling technique, each material (block and mortar) was represented by its own mechanical properties. The validation of numerical models was based on experimental results. It was found that the obtained numerical values of compressive strength and modulus of elasticity differ by 5% from the experimentally observed values. Moreover, mechanisms responsible for the rupture of the prisms were evaluated and compared to the behaviors observed in the tests and those described in the literature. Through experimental results it is possible to conclude that the numerical models have been able to represent both the mechanical properties and the mechanisms responsible for failure.

scholarly journals Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein

Cell ◽  
2021 ◽  
Author(s):  
Naveenchandra Suryadevara ◽  
Swathi Shrihari ◽  
Pavlo Gilchuk ◽  
Laura A. VanBlargan ◽  
Elad Binshtein ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Spike Protein ◽  
Human Monoclonal Antibodies ◽  
Terminal Domain

scholarly journals Monoclonal antibodies prepared against Dictyostelium actin: characterization and interactions with actin.

1984 ◽  
Vol 99 (1) ◽  
pp. 287-295 ◽  
Author(s):  
P A Simpson ◽  
J A Spudich ◽  
P Parham
Keyword(s):  
Monoclonal Antibodies ◽  
Antigenic Site ◽  
Amino Acid Sequences ◽  
Cellular Slime Mold ◽  
Antigenic Sites ◽  
Critical Residue ◽  
Slime Mold Dictyostelium Discoideum ◽  
Cellular Slime ◽  
B Lymphoid ◽  
Alpha Actins

Three mouse monoclonal antibodies, Act I, Act II, and Act IV, against actin from the cellular slime mold Dictyostelium discoideum, have been made and characterized. All three antibodies are IgG1 and share the following properties: They form stable complexes with monomeric Dictyostelium actin, which prevents polymerization of the actin into filaments. On addition to preformed actin filaments, they cause a reduction in filament size and in the viscosity of the actin solution. They cross-react strongly with actins from the lower eucaryotes Physarum and Acanthamoeba, but not with alpha-actins from rabbit and human muscle or beta- and gamma-actins from human erythrocytes and a human B lymphoid cell line. Act II and Act IV recognize a similar antigenic determinant that is topographically distinct from that identified by Act I. In protein immunoblotting, only Act I bound strongly to Dictyostelium actin. Analysis of actin fragments with this technique showed that amino acids 13 to about 50 are required for Act I binding to actin. A comparison of the amino acid sequences of actins from lower eucaryotes and higher vertebrates implicates threonine 41 as a critical residue in the Act I antigenic site. The properties of Act II and Act IV suggest that they recognize antigenic sites involving the NH2-terminal six residues.

Reactions of human antibodies with CR1 immobilised by mouse monoclonal antibody E11 Red cell phenotype Murine MAb Human anti- Absorbance Ratio Kn(a+) ] Kn(a-) E11 Kna 0.755 0.195 4:1 McC(a+) 0.538 McC(a-) E11 McC 0.136 4:1 Yk(a+) 0.315 Yk(a-) E11 Yka 0.120 26:1 Sl(a+) 0.342 Sl(a-) E11 Sla 0.074 4.6:1 Cs(a+) 0.139 Cs(a-) E11 Cs 0.108 Mapping relative positions of antigens on a specific protein When several murine monoclonal antibodies to different epitopes on the same protein are available, MAIEA can be used to study the relative position of antigens on that protein. This application of MAIEA depends on mutual inhibition of murine monoclonal antibodies and human antibodies. A negative result is obtained when human and monoclonal antibodies compete for the same epitope, or bind to very closely located epitopes, so no tri-molecular complex is produced. Several monoclonal antibodies to the Kell protein have been used in MAIEA to study the relationships of the Kell system antigens [10]. The decay accelerating factor DAF, CD55, is detected by several monoclonal antibodies. Three antibodies BRIC 230, BRIC 110 and BRIC 216 were known from competitive binding assays to bind to different short consensus repeats (SCR) [11]. So three of the four SCRs of the DAF molecule were positively identified (Table II). Strong positive reactions were observed with all three BRIC antibodies and anti-Cr3, anti-WES8, and anti-WESb showing that MAIEA is a useful techique for studying this system [12]. The results showed that Cr8, WESa, and WESb are not on the first three SCRs and must

1995 ◽  
pp. 190-190
Keyword(s):  
Monoclonal Antibody ◽  
Monoclonal Antibodies ◽  
Molecular Complex ◽  
Specific Protein ◽  
Cell Phenotype ◽  
Binding Assays ◽  
Human Antibodies ◽  
Short Consensus Repeats ◽  
Murine Monoclonal Antibodies ◽  
Competitive Binding Assays
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