The Versatility of Multiplex Antibody Titer Assays for COVID-19 and Beyond

 

The COVID-19 outbreak that began in Wuhan, China in December 2019 was marked by an increase in the number of cases showing pneumonia-like symptoms.^1,2 It was not until about a month after the outbreak began that genomic analysis identified a novel coronavirus as the causative agent. With the emergence of new pathogen strains, genomic assays are not always able to detect new variants, and after an infection, may not be able to identify which pathogens were involved. However, with serological assays that pick up polyclonal antibody responses, the conservation of epitopes—even with new variants—make it possible to identify the different pathogens circulating in an epidemic.

While genomic tests can be modified to distinguish between different pathogen strains once they are identified, the identification of causative agents during and post- epidemics can be better determined with serological assays. This would be especially useful when screening patients for COVID-19, which presents with flu- or pneumonia-like symptoms—similar to infections caused by other respiratory pathogens.^3-5 An assay that can determine which pathogens are eliciting immune responses in patient populations would provide significant value for triaging patients into appropriate treatment categories. Post-pandemic, this type of serological assay could not only more precisely identify the causative pathogens that have passed through, or are still passing through a population, it could also monitor the pathogens involved in second waves of infection.

With Luminex’s xMAP® bead-based platforms, multiplex serological assays can be developed for this type of immune surveillance of different pathogens, as well as for vaccine testing and developing immune therapies.^6-10 The process of coupling antigens to Luminex beads is simple and can be completed in a few hours. By multiplexing, an assay that could distinguish antibody titers of a number of different pathogens in a single reaction with very small sample volumes would enable clinicians to determine the causative pathogen(s) of a patient’s illness within a few hours.

These types of multiplex immune surveillance assays would be beneficial for other diseases with similar clinical symptoms as well. Examples include hemorrhagic fevers that are caused by viruses from several viral families, as well as chronic fatigue syndromes, which can be caused by a number of different viral, bacterial, and microbial pathogens—to name a few.^11,12

With its multiplexing ability to measure antibody titers to multiple antigens in one reaction, Luminex xMAP® Technology provides the ideal platform for building these types of multiplex serological assays. For more information on Luminex assay development, download the xMAP® Cookbook. Luminex also offers custom assay development services through LuminexPLORE Lab.

For genomic assay screening, Luminex has several platforms that can screen for multiple pathogens involved in both respiratory and gastrointestinal infections, in addition to food safety applications. Information about Luminex diagnostic assays can be found on our webpage.

Stephen Angeloni, PhD, is a Senior Field Application Scientist at Luminex Corporation.

References

1. Dong E, Du H, and Gardner L. An interactive web-based dashboard to track COVID-19 in real time. The Lancet Correspondence. February 2020.
2. Ding Q, Lu P, Fan Y, et al. The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China. J Med Virol. 2020 Mar. doi: 10.1002/jmv.25781.
3. Centers for Disease Control and Prevention. Causes of Pneumonia. March 2020. Accessed March 2020. Available from: https://www.cdc.gov/pneumonia/causes.html.
4. The World Health Organization. Pneumonia Fact Sheet. August 2019. Accessed March 2020. Available from: https://www.who.int/news-room/fact-sheets/detail/pneumonia.
5. The Mayo Clinic. Pneumonia. March 2018. Accessed March 2020. Available from: https://www.mayoclinic.org/diseases-conditions/pneumonia/symptoms-causes/syc-20354204.
6. Khaliq A, Ravindran R, Hussainy S, et al. Field evaluation of a blood based test for active tuberculosis in endemic settings. Plos One. https://doi.org/10.1371/journal.pone.0173359.
7. Trivedi S, Miao C, Sanchez J, et al. Development and Evaluation of a Multiplexed Immunoassay for Simultaneous Detection of Serum IgG Antibodies to Six Human Coronaviruses. Scientific Reports. February 2019.
8. Elberse K, de Greef S, Wattimena N, et al. Seroprevalence of IgG antibodies against 13 vaccine Streptococcus pneumoniae serotypes in the Netherlands. Vaccine Volume 29, Issue 5, 29 January 2011, Pages 1029-1035. https://doi.org/10.1016/j.vaccine.2010.11.054.
9. Opalka D, Lachman C, MacMullen S, et al. Simultaneous Quantitation of Antibodies to Neutralizing Epitopes on Virus-Like Particles for Human Papillomavirus Types 6, 11, 16, and 18 by a Multiplexed Luminex Assay. Clin Diagn Lab Immunol. 2003 Jan; 10(1): 108–115. doi: 10.1128/CDLI.10.1.108-115.2003.
10. Berglund J, Vink P, Tavares Da Silva F, et al. Safety, immunogenicity, and antibody persistence following an investigational Streptococcus pneumoniae and Haemophilus influenzae triple-protein vaccine in a phase 1 randomized controlled study in healthy adults. lin Vaccine Immunol. 2014 Jan;21(1):56-65. doi: 10.1128/CVI.00430-13.
11. Centers for Disease Control and Prevention. Viral hemorrhagic fevers (VHFs). January 2014. Accessed March 2020. Available from: https://www.cdc.gov/vhf/index.html.
12. Centers for Disease Control and Prevention. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. July 2018. Accessed March 2020. Available from: https://www.cdc.gov/me-cfs/about/possible-causes.html.