Multiplexed SARS-CoV-2 Platforms: Future Interactions

Recorded Webinar: Assessment of the Humoral Response to SARS-CoV-2 Infection Via Novel Multiplexed Assays

Guest speaker: E. Steve Woodle of UC Health in Cincinnati, Ohio

Current data suggests that COVID-19 patients may present with a myriad of antibody responses. Dr. E. Steve Woodle with the University of Cincinnati College of Medicine believes that determining the nature of these varied antibody responses, as well as coordinating that data with clinical outcomes, will be key to understanding the nature of the SARS-CoV-2 virus. In this talk, Dr. Woodle reviews the body of evidence that suggests this virus may circumvent many of the typical rules of immune response and discusses the research applications for a multiplex assay as a tool for exploring how a patient’s antibody response impacts the severity of their case.

 

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Key Takeaways

  • Testing for multiple SARS-CoV-2 targets with the One Lambda™ LABScreen™ COVID Plus Assay can increase the accuracy of post-vaccination antibody tests in transplant laboratories. 
  • Specific: Antibodies against the SARS-CoV-2 spike and nucleocapsid proteins are detected with 100% specificity in the presence of antibodies to common cold viruses. 
  • Sensitive: SARS-CoV-2 antibody profiles can be generated for transplant patients with impaired antibody responses to identify patients who are more likely to become severely ill. 
  • Accurate: Multiplexing reduces the number of false-positive and false-negative test results.

Overview

SARS-CoV-2 has had a significant impact on transplant patients who are immunosuppressed because they are more susceptible to infection. Detecting and quantifying antibodies to the virus is critical to accurately assess the risk of transplant procedures for these patients, but they often have impaired antibody responses. In addition, cross-reactivity with common cold viruses can generate false positives. A better assessment of an antibody profile can be made by taking a multiplexing approach since it reduces the potential for false negatives and false positives.

Multiplex Testing

To address the unmet need for a multiplex COVID-19 assay, researchers at Emory University, the University of Cincinnati, Stanford University, and the University Health Network in Toronto collaborated with scientists at Thermo Fisher Scientific to develop the LABScreen COVID Plus Assay. With Luminex® xMAP® technology and a One Lambda™ LABScan™ 100 or LABScan3D™ System, results can be obtained in just a few hours. Multiplex testing with the LABScreen COVID Plus Assay is more efficient and cost-effective than testing individual targets, and it is less likely to generate false positives and false negatives.

The LABScreen COVID Plus Assay can be used to detect antibodies after vaccination, which is particularly important for immunosuppressed patients who may have a reduced vaccine response. The assay can be utilized to detect and quantify antibodies after vaccination in patients who are undergoing passive prophylaxis. It can also be used to determine the nature of a patient’s antibody response.

The assay has a comprehensive SARS-CoV-2 multiplex antibody detection panel that includes:

  • Antibodies that target the SARS-CoV-2 spike trimer, S1 subunit, S2 subunit, receptor-binding domain (RBD), and the SARS-CoV-2 nucleocapsid protein 
  • Four antibodies that target spike proteins on common cold coronaviruses 
  • Antibodies that target MERS and SARS spike proteins

With the LABScreen COVID Plus Assay, researchers can:

  • Confirm and benchmark previous SARS-CoV-2 infection 
  • Eliminate false negatives with broader antigen coverage than single or duplex detection 
  • Differentiate antigenicity along the spike and nucleocapsid proteins to identify both therapeutic and potentially detrimental antibody responses 
  • Monitor quantitative changes in antibody profiles after vaccination or infection 
  • Distinguish between vaccine-induced immunity and the efficacy of the humoral response over time to determine whether a booster will be needed

Future Applications: Understanding Heterogeneity in the Antibody Response

The antibody responses of symptomatic and asymptomatic individuals infected with SARS-CoV-2 differ, as do those of survivors and individuals who die as a consequence of infection. Heatmaps of antibodies in individuals who have been infected with the virus show that seroconversion to IgM antibodies can occur before or after IgG seroconversion, and simultaneous conversion is possible. This indicates that the antibody response to SARS-CoV-2 does not always follow the usual pattern of an early IgM spike with a subsequent IgG spike. Other antibodies can be added to the LABScreen COVID Plus Assay panel to obtain valuable information about the nature of the antibody response. For example, IgG antibodies that target the structural proteins orf8 and orf3B are accurate serological markers of early- and late-stage SARS-CoV-2 infection. The assay could also be used to investigate nonstructural proteins and mutated versions of the RBD, which could help researchers determine whether such mutations affect antibody response. Functional analyses to investigate antibody isotype, subclass, FcR binding capacity, and complement binding capacity could be incorporated into the assay. This type of analysis would provide valuable information about the global antibody response to SARS-CoV-2.