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SARS-CoV-2 Neutralizing Antibodies

Neutralizing antibodies are of particular interest to scientists. They efficiently stop the infection by blocking the interaction between the SARS-CoV-2 virus and the host cells. Most neutralizing antibodies respond to the receptor binding domain (RBD) of the spike protein, which binds directly to the cell surface receptor ACE2. antibodies-online currently offers two NAbs based on clone CR3022.

CR3022 Antibody ABIN6952546 not affected by B.1.1.7 (alpha), B.1.351 (beta), B.1.617.1 (kappa), B.1.617.2 (delta) and P.1 (gamma) Mutations

Fig. 1: Microscale thermophoresis measurements of binding of SARS-CoV-2 Spike S1 antibody (RBD) CR3022 (ABIN6952546) to SARS-CoV-2 Spike (Trimer) from wt SARS-CoV-2 (ABIN6952670) or variants B.1.1.7 alpha (ABIN6963742), B.1.351 beta (ABIN6963740), P.1 gamma (ABIN6964443), B.1.6172 delta (ABIN6999328), B.1.429 epsilon (ABIN6972926), B.1.525 eta (ABIN6972924), and B.1.617.1 kappa (ABIN6976302) The determined dissociation constants KD are indicated.

One of the looming questions regarding newly emerging variants of SARS-CoV-2 is, whether existing antibody based assays and pharmaceuticals remain useable. In collaboration with Nanotemper we measured the affinity of our S protein RBD antibody CR3022 (ABIN6952546) to the canonical trimeric SARS-CoV-2 S protein and those of the variants of concern B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), B.1.617.1 (kappa) and P.1 (gamma). by microscale thermophoresis (MST). These measurements will be extended to additional antibodies and protein variants in the near future.

A higher dissociation constant is indicative of a weaker binding, i.e. CR3022 binding of the B.1.351 S protein is significantly weaker than of the other three variants. However, a KD in the nanomolar range does indicate a high affinity of the antibody to all four tested S proteins. Accordingly, the neutralizing antibody remains an important tool for SARS-CoV-2 immunoassays. Our SARS-CoV-2 Mutations Tracker keeps you updated about new products relevant for research on novel SARS-CoV-2 variants.

Available SARS-CoV-2 Neutralizing Antibodies based on Clone CR3022

Product
Clonality
Clone
Isotype
Source
Cat. No.
Validations
Quantity
Datasheet
ClonalityMonoclonal
CloneCR3022
IsotypeIgG1 kappa
SourceHuman
Cat. No.ABIN6952546
Validations
  • (9)
  • collections(13)
Quantity200 μg
ClonalityChimeric
CloneCR3022
IsotypeIgG kappa
SourceRabbit
Cat. No.ABIN6952547
Validations
  • (7)
  • collections(3)
Quantity200 μg

Binding of S Protein from other SARS-CoV-2 variants

The SARS-CoV-2 S Protein is essential for the virions’ contact to the host cell via the ACE2 receptor. ACE2 contact points are situated between amino acids K417 and Y505 of the S Protein Receptor Binding Domain (RBD). Neutralizing antibodies (nAbs) targeting the RBD disrupt this interaction and can thus impede SARS-CoV-2 interaction. Based on the known contact points of the neutralizing antibody CR3022 with the S protein we had predicted that the antibody would still bind the protein from variants of concern B.1.1.7, B.1.351, and P.1.6,7,8,9

This prediction was confirmed by the MST measurements. It is also reasonable to assume that CR3022 will bind the B.1.617 variant S protein as well as the S proteins from other variants of interest. We are currently working on corresponding experiments.

Fig. 2: Mutations (indicated in red) in the SARS-CoV-2 S Protein receptor binding domain (RBD, mint) in variants of concern (light grey) and variants of note (light mint). Epitopes of the neutralizing antibody CR3022 ABIN6952546 are highlighted in yellow.6,7,8,9

Neutralizing Antibodies

A part of antibodies produced during an immune response are neutralizing antibodies (NAbs). NAbs can inhibit the infectivity binding specifically to surface structures, thus preventing the interaction with its host cells. NAbs are used for passive immunization and also play a role in active immunization by vaccination.

The antibody clone CR3022 (ABIN6952546), which is the basis for both antibodies, was originally isolated from a convalescent SARS patient from Singapore1. The clone was demonstrated to be effective in neutralization assays for different SARS-CoV strains in synergy with other RBD-targeting antibodies. Its epitope does not overlap with the angiotensin-converting enzyme 2 (ACE2) binding site, thus leaving it accessible for other neutralizing antibodies. Since the outbreak of COVID-19, CR3022 has been demonstrated to bind the SARS-CoV-2 S protein RBD in a similar fashion2. Crystallization assays of CR3022 bound to its SARS-CoV-2 target have provided important insights into possible attack points for therapeutics against this virus3. Moreover, CR3022 has been used as a positive control in serological assays to detect antibodies in human serum that bind SARS-CoV-2 S-protein4.

One of the many advantages of recombinant Antibodies with human IgG-structures like the Spike Protein Antibody (ABIN6952546) or the N Protein Antibody (ABIN6952664) is that they can be used as standards in the development of assays for the detection of human IgGs against SARS-CoV2.

Please note: We can provide the humanized Spike-protein antibody (ABIN6952664) (IgG1) in various isotypes. If you have special interest please contact our customer service.

Mechanism of action of monoclonal antibodies for viral infection

Fig.3: Monoclonal antibodies can directly interfere with viral pathogenesis in multiple ways. First, binding of a neutralizing antibody to the virion can prevent target cell binding and/or fusion. Furthermore, antibody binding opsonizes the virions or infected cells for phagocytic uptake. If viral proteins are intercalated into target cell membranes during viral egress, monoclonal antibodies can facilitate target cell death via complement fixation and membrane attack complex (MAC) activation or antibody-dependent cytotoxicity. These mechanisms may result in apoptosis or necrosis of the infected cell.10

Product
Clonality
Clone
Isotype
Source
Cat. No.
Validations
Quantity
Datasheet
ClonalityMonoclonal
CloneCR3022
IsotypeIgG1 kappa
SourceHuman
Cat. No.ABIN6952546
Validations
  • (9)
  • collections(13)
Quantity200 μg
ClonalityChimeric
CloneCR3022
IsotypeIgG kappa
SourceRabbit
Cat. No.ABIN6952547
Validations
  • (7)
  • collections(3)
Quantity200 μg

Discover our SARS-CoV-2 Mutations Tracker

Stay up to date re mutation specific antibodies, proteins, assays

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References

  • (1) ter Meulen, J. et al. Human monoclonal antibody combination against SARS coronavirus: synergy and coverage of escape mutants. PLoS Med. 3, e237–e237 (2006).
  • (2) Tian, X. et al. Potent binding of 2019 novel coronavirus spike protein by a SARS coronavirus-specific human monoclonal antibody. Emerg. Microbes Infect. 9, 382–385 (2020).
  • (3) Yuan, M. et al. A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV. Science 80eabb7269 . doi:10.1126/science.abb7269 (2020).
  • (4) Stadlbauer, D. et al. SARS-CoV-2 Seroconversion in Humans: A Detailed Protocol for a Serological Assay, Antigen Production, and Test Setup. Curr. Protoc. Microbiol. 57, e100 (2020).
  • (5) Thao, T. et al. Rapid reconstruction of SARS-CoV-2 using a synthetic genomics platform Nature.   (2020).
  • (6) Barnes CO et al. SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies. Nature (2020). doi:10.1038/s41586-020-2852-1
  • (7) Cheng MH et al. Impact of South African 501.V2 Variant on SARS-CoV-2 Spike Infectivity and Neutralization: A Structure-based Computational Assessment. bioRxiv 2021.01.10.426143 (2021). doi:10.1101/2021.01.10.426143
  • (8) Garcia-Beltran WF et al. Circulating SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. medRxiv 2021.02.14.21251704 (2021). doi:10.1101/2021.02.14.21251704
  • (9) Yuan M et al. A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV. Science 368, 630–633 (2020).
  • (10) Taylor, P.C., Adams, A.C., Hufford, M.M. et al. Neutralizing monoclonal antibodies for treatment of COVID-19. Nat Rev Immunol (2021). https://doi.org/10.1038/s41577-021-00542-x
  • (11) Emily Engelhart, Randolph Lopez, Ryan Emerson, Charles Lin, Colleen Shikany, Daniel Guion, Mary Kelley, David Younger. Massively Multiplexed Affinity Characterization of Therapeutic Antibodies Against SARS-CoV-2 Variants. Preprint. bioRxiv 2021.04.27.440939; doi: https://doi.org/10.1101/2021.04.27.440939
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