COVID-19 RESOURCES

Enabling the discovery of vaccines and anti-viral therapeutics against SARS-CoV-2

Virology Experience

Deep expertise in virology is at the core of Integral Molecular’s 20-year history. Our technologies and R&D services enable over 300 companies working in vaccine research and drug discovery, and have been published in over 200 peer-review publications including in Cell, Science, and Nature. Scientists at Integral Molecular have been on the forefront of combatting viral epidemics including Zika, Ebola, Chikungunya, and now SARS-CoV-2.

SARS-CoV-2 Reporter Virus Particle Offerings for Neutralization Assays

Integral Molecular offers quality-controlled SARS-CoV-2 reporter virus particles (RVPs) that enable safe (BSL-2), easy, and high-throughput viral infectivity and neutralization assays using standard detection instrumentation. RVPs are designed to be antigenically identical to wild-type viruses but with a modified genome that expresses a convenient optical reporter gene (GFP or luciferase) upon cellular infection. To assess the breadth of neutralization, we offer SARS-CoV-2 (Wuhan-Hu-1 and D614G), SARS-CoV-1 and MERS-CoV RVPs in addition to custom strains.

RVPs are available as validated, ready-to-use reagents that provide an efficient and safe (replication-incompetent) alternative to plaque assays. Dozens of commercial and academic laboratories use our RVP systems, for both R&D (e.g. for rapid testing of escape mutations and strain variants) and for serum sample testing (e.g. in vaccine clinical trials as critical reagents). As part of our commitment to supporting COVID-19 research, we are providing access to free SARS-CoV-2 RVP trial samples.

See application note

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Epitope Mapping Coronavirus MAbs

Integral Molecular is the industry leader in high-throughput epitope mapping of anti-viral MAbs, having mapped over 1,000 viral epitopes. Our Shotgun Mutagenesis epitope mapping platform allows us to rapidly map neutralizing or non-neutralizing MAbs, even for conformational epitopes, at single-amino-acid resolution. These epitope maps help determine the mechanism of action for each MAb, identify best therapeutic candidates, design MAb cocktails, and define how vaccines and the natural human immune system can effectively neutralize the virus.

Learn more about Shotgun Mutagenesis

MAb Specificity Testing and Identification of New Coronavirus Receptors

The Membrane Proteome Array (MPA) consists of 94% of the human membrane proteome (~6,000 proteins) in its native conformation, arrayed for binding or functional studies on live cells. The MPA is being actively used by over 100 different companies to test their therapeutic MAbs for specificity and safety prior to entering preclinical trials. The MPA has also been used to successfully identify new receptors and attachment factors for Dengue, Zika, Ebola, and Marburg viruses

Learn more about our Membrane Proteome Array

Vaccine and Protein Engineering SARS-CoV-2 Spike Protein

High-throughput protein engineering is behind many of Integral Molecular’s technologies. Using live cell functional screening of mutation libraries (hundreds to thousands of point mutations and/or chimeras), we identify individual amino acids or regions important for viral envelope functions, such as expression, protein folding, trafficking, budding, infectivity, and immunogenicity. As a result, we have identified vaccine variants with improved characteristics for HIV, dengue, zika, HCV, and Ebola viral envelope proteins.

Learn more about our experience with protein engineering

SARS-CoV-2 Reporter Virus Neutralization Assays Webinar

Learn how our SARS-CoV-2 RVPs are used to detect neutralizing antibodies

Frequently Asked Questions

RVPs

What strains or isolates are the RVP spike proteins based on?

SARS-CoV-2: Wuhan Hu-1
SARS-CoV-2: Wuhan Hu-1 D614G
SARS-CoV-1: Urban
MERS-CoV: HCoV-EMC

Custom RVPs can be made using spike with specified mutations or specific strains.

What reporter gene is used to quantify RVP infectivity.

The RVPs are available with a GFP or Renilla luciferase reporter.

Do the RVPs measure neutralization by patient sera?

All antibody neutralizing responses that block viral infectivity will be detected by this assay. This includes patient sera and purified antibody (IgG, IgM, IgA).

Are antibodies that cross react with other coronaviruses detected by the RVP assay?

It is possible that antibodies that neutralize SARS-CoV-2 RVPs cross react with additional coronaviruses. SARS-CoV-1 and MERS RVPs are also available from Integral Molecular and can be used to test for cross reactivity.

Do you provide cells with the RVPs? What cells do you recommend?

We provide a clonal stable HEK-293T ACE2 cell line that can be robustly infected by the RVPs. Other permissive cell lines can be used, however in our hands cell lines such as Vero cells result in lower signals.

Can I bank the ACE2 stable HEK293T cells or are they supplied for one-time usage?

Yes, you are welcome to bank the cells for your own use with RVPs. We ask that you not distribute these cells to others or use them for unrelated applications.

Should I use GFP or luciferase RVPs?

We recommend either GFP or luciferase RVPs depending on your instrumentation and how you wish to quantitate virus infectivity.

GFP output is calculated as a percentage of infected cells and is easy to visualize. GFP detection requires a microscope, high-content imager, or flow cytometer.
Luciferase is more sensitive, has a higher signal:background and is generally faster to detect. However, individual infected cells cannot be counted using this method. Luciferase detection requires the use of a consumable substrate and a luminometer to read plates.

How bright is the green fluorescent reporter?

The fluorescent protein is eGFP. It can be easily seen under a microscope and detected by flow cytometry.

What assay reagent do you recommend using with the luciferase RVPs?

The reporter is Renilla luciferase, so only reagents compatible with Renilla luciferase should be used. We recommend the Promega Renilla-Glo® Luciferase assay system (E2710) because it gives a stable signal, high signal:background, and high Z’. Note: for optimal detection reproducibility, you should wait 5-minutes after adding the reagent to read.

Can the RVPs be used in membrane fusion experiments?

The RVPs are not designed for lipid or content mixing based fusion assays. The RVPs are designed to measure viral entry into cells and express a reporter gene once inside the cell.

Can the samples be freeze-thawed?

We do not recommend repeated freeze-thaw of the RVPs. However, it is possible to thaw and aliquot the RVPs upon receipt without an appreciable loss of titer. We recommend using a flash freeze protocol if possible, such as a dry ice-ethanol bath or liquid nitrogen.

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