SARS-CoV-2 Spike 1 Protein Monoclonal Antibodies and Antigens for Serologic Assays
SARS-CoV-2 Antigens for Sensitive and Specific Serologic COVID-19 Assays
Serological diagnosis of COVID-19 is becoming an important tool to understand the extent of COVID-19 in the community however the assay must not have cross-reactivity to other coronaviruses to be effective. The most sensitive and earliest serological marker is total antibodies produced against SARS-CoV-2. The majority of the antibodies generated will be against the nucleoprotein which is the most abundant protein of the virus and tests that detect IgG/IgM to the nucleoprotein would relatively be the most sensitive. However, the RBD domain of the S-protein is the host attachment protein, and antibodies to RBD would be more specific and are expected to be neutralizing. (Sethuraman, N. et al (2020). Interpreting Diagnostic Tests for SARS-CoV-2. AMA. 323(22):2249-2251). To broaden an assay’s coverage and increase the sensitivity and specificity, several diagnostics manufacturers are starting to use several antigens (e.g. N, S1, RBD) within a single assay. In addition, an antigen complex consisting of RBD/ACE2 might further increase assay specificity as studies have shown that the binding of SARS-CoV-2 S protein to ACE2 might provoke a change in its three-dimensional structure exposing new immunogenic sites for antibody binding (Cuffari, B. How does a SARS-CoV-2 Virion Bind to ACE2? Retrieved from: News-Medical.Net).
Antigens for Total Antibody COVID-19 Assays
|rec-SARS-CoV-2 Spike Protein|
|9558||SARS-CoV-2 Spike S1 RBD Protein|
|9552||SARS-CoV-2 Spike S1 RBD Protein|
|9556||SARS-CoV-2 Spike protein, S1 subunit|
|9557||SARS-CoV-2 Spike S1 NTD|
|9560||SARS-CoV-2 full length Nucleocapsid|
Novel SARS-CoV-2 Trimeric Spike 1 Protein Monoclonal Antibodies
FDA approved rapid antigen diagnostics (RADs) for COVID-19 rely upon nasal swabs for the detection of the SARS-CoV-2 nucleoprotein. However new tests are in development for the detection of the SARS-CoV-2 spike protein in saliva and are potentially capable of detecting early infections in asymptomatic individuals.
Meridian’s new monoclonal antibody pair to SARS-CoV-2 S1 trimeric protein is capable of recognizing the spike 1 (S1) protein regardless of its conformation state (e.g. “up” or “down”). The antibodies bind to a linear epitope on the trimeric S1 protein that is distinct from the RBD protein, which has epitopes that are conformation-dependent. Recent studies have shown that linear epitopes on the trimeric S1 protein are able to elicit neutralizing antibodies in COVID-19 patients and have potent antigenicity, making them prime targets for diagnostic, therapeutic and vaccine targets.
The SARS-CoV-2 spike protein is located on the virus surface and it is responsible for binding to the ACE2 receptor of target cells and mediating subsequent viral uptake and fusion. It is first produced as a trimeric precursor and requires cleavage into two fragments by furin-like proteases for activation: The N-terminal receptor-binding fragment S1 that contains the receptor-binding domain (RBD) protein, and the C-terminal fusion fragment S2. The RBD protein is responsible for ACE2 receptor binding and exists in two conformational states; the “down” form where the receptor binding site is inaccessible, or “up” form where it exposes the ACE2 receptor binding site. These two forms (open or closed) may induce different ranges of antibodies in the host and it is speculated that this may be a way the virus protects itself and shifts the host response towards non-neutralizing antibodies.