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SARS-CoV-2 trimeric spike proteins, available in grams.

ExcellGene scientists have generated a stable, clonally derived, recombinant, suspension grown CHO cell line that produces a secreted, stabilized version of the trimeric spike protein of SARS-CoV-2.

When the first genome sequences of the virus were released, ExcellGene recognized the market need for large quantities of the virus’ spike proteins. Our first successful production of “Wuhan” spikes in CHO cells – in a “trimeric” structure by using mutations that lock the protein in the “pre-fusion” form – became available in gram quantities in May 2020.

Since then, experimental vaccines containing ExcellGene’s proteins have been found to be highly immunogenic in mice, rabbits, and horses (pre-publication released November 2021). One of the vaccines was shown to be protective against SARS-CoV-2 in a hamster-model (publication under review). Neutralizing antibodies elicited by the vaccine were shown to be long-lasting (>280 days in mice) and highly cross-reactive against Alpha- and Beta pseudoviruses. Since this first success, subsequent work has yielded Alpha, Beta, and Delta variant trimeric spike proteins exhibiting similar properties – highly immunogenic with long-lasting antibodies [see publications].

ExcellGene’s GMP-ready manufacturing process is fully scalable and uses only chemically defined components. The secreted spike protein accumulates in the protein-free cell culture fluid of the cells.

This approach results in high quality and high purity proteins in a stable formulation that do not require ultra-low temperature for long-term storage or transport. These qualities make the proteins optimal for diagnostics/testing applications, R&D, and drug and vaccine development.

Many variants are available in mg to gram quantities, as shown below:

Stabilized Delta Trimeric Spike Protein (mg-g)

The Delta variant of SARS-CoV-2 was first detected in India and has, by November 2021, spread to over 179 countries. It contains a 614G mutation and others, notably a proline to arginine substitution that may facilitate the cleavage of the S precursor into the S1/S2 conversion, which results in the fusion of the spike protein with the cell membrane receptor ACE2.

Stabilized Beta Trimeric Spike Protein (mg-g)

The Beta variant – initially found in South Africa — shows additional mutations in the spike protein, the most important ones as K417N, E484K and N501Y (the last one was found already in the Alpha variant). Also, the D614G mutation remains in this variant.

Stabilized Alpha Trimeric Spike Protein (mg-g)

The Alpha variant, also known as B.1.1.7., emerged as a variant of concern (VOC) after a mutation in the spike protein D614G and was recognized as possibly more infectious to people. The Alpha variant carries other mutations, such as N501Y, and is considered 40 to 80% more transmissible than the original “Wuhan” strain.

Stabilized Omicron Trimeric Spike Protein (mg-g)

The Omicron variant became known to the general public recently in end of November 2021 and is characterized by many mutations in the Spike protein and other regions of the virus genome. It seems to spread even more rapidly than the Delta variant, and questions about the protection against this variant by current vaccines have been raised. This variant may have an increased capacity to re-infect vaccinated people.

sStabilized Wuhan Trimeric Spike Protein (mg-g)






Product: Stabilized Wuhan Trimeric Spike Protein
Modifications C-terminal Transmembrane region replaced with a trimerization domain and a polyhistidine tag. Two stabilizing proline mutations and scrambled S1/S2 furin cleavage site
Isolate (Seq ID) Wuhan-Hu-1 (GenBank: MN908947)
Expression System CHOExpress® cells
Purity >95 % as determined by SDS-PAGE
Buffer 0.01M PBS, pH 7.4, no preservatives

Receptor binding domain (RBD), monomeric (mg-g)

Additionally, we offer the RBD domain produced in the same CHO cell system. The RBD protein is located in the S1 part of the spike protein and is easier to produce and purify because of its’ small size. This makes it an ideal alternative for applications where costs are the driving factor. Please contact us to learn about our pricing per gram or mg of RBD protein.




Product: Receptor binding domain (RBD) SARS-CoV-2, monomeric
Modifications C-terminal extended with a strep and a polyhistidine tags.
Isolate (Seq ID) Wuhan-Hu-1 (GenBank: MN908947)
Expression System CHOExpress® cells
Purity > 95 % as determined by SDS-PAGE
Buffer 0.01M PBS, pH 7.4, no preservatives

On spike proteins of SARS-CoV-2 variants

The rapid emergence of virus variants has surprised the scientific community and the general public. Most mutations occur within the gene sequence encoding the spike protein.

We have made it an ongoing priority to develop and produce spike proteins of variants as they appear, in order to help the scientific community understand the nature and impact of these protein structures.

ExcellGene scientists optimized the variant spikes to stabilize their structure in the so-called “pre-fusion” conformation. They are free of any tag sequences (‘HIS’ or other), which are often used to facilitate purification. Instead, we developed a highly efficient affinity step to capture the protein directly from the supernatant of cultures from the production bioreactors.

For more detailed information on mutations of SARS-CoV-2 variants, consult the Stanford SARS-CoV-2 Variants Genome Viewer, a tool which visually depicts the most critical mutations in the SARS-CoV-2 genome.

Diagnostic applications

It is now well established that antibodies directed against SARS-CoV-2 can protect an individual against COVID-19. Diagnostic tests that detect and quantify these antibodies in blood or saliva are a vital tool for clinicians to answer important questions:

  • Has an individual gone through an infection (possibly a-symptomatic)?
  • Has an individual responded immunologically to exposure with a vaccine candidate?
  • Does an individual have antibody levels that are high enough to protect against (re)infection?

To protect against SARS-CoV-2, a patients’ antibodies need to be directed against critical parts of the virus. In fact, hospitalized patients that have antibodies mainly directed towards the ‘wrong’ part of the virus (the Nucleocapsid protein) were shown to be more likely to die [1]. The most efficient antibodies against the virus are so-called neutralizing antibodies, which seem to be exclusively directed against the Spike protein [9].

Antibody levels in hospitalized COVID-19 patients are generally high and fairly easy to detect. In contrast, these levels are much lower in people that have resolved the infection with little or no clinical symptoms. It is reasonable to expect that similar, low levels of antibodies are to be expected in response to vaccination.

Because low levels of antibodies against the SARS-CoV-2 spike can protect an individual against COVID-19, it is essential that diagnostic tests have sufficient sensitivity to detect low levels of antibodies.

The ideal diagnostic test for SARS-CoV-2 antibodies would be one that is able to detect all antibodies directed against the spike protein. To do this, one would need to produce highly purified spike proteins in its ‘natural’ conformation.

This turned out to be problematic; the monomeric spike protein is large (150 kD), heavily glycosylated and inherently unstable. The protein is readily cleaved by furin-proteases and it can change conformation easily. To make matters worse, the spike is presented on the virus particle as a homo-trimer complex; however, the monomers are not covalently bound to each other.

Current diagnostic tests lack the sensitivity to detect low levels of antibodies

Because of these issues, currently available tests were developed on the basis of fragments of the spike protein to detect antibodies against SARS-CoV-2 [12, 13, 3, 7]. Recently, a version of the spike protein was developed and published [5, 14] that appears more stable, forms trimers and is also glycosylated [11].

This stabilized trimeric protein was used as a template for many of the SARS-CoV-2 vaccine candidates (Novavax, Moderna, Pfizer/BioNTech, GSK/Clover, CureVac and others) either as an encoding RNA molecule, presented on a virus-vector or as subunit protein based vaccine concept.

Useful links to webpages that track the development of COVID-19 vaccines and treatments: Milken Institute Covid-19 Treatment and Vaccine Tracker and NYTimes Coronavirus Vaccine Tracker.


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