Utility of Different Surrogate Enzyme-Linked Immunosorbent Assays (sELISAs) for Detection of SARS-CoV-2 Neutralizing Antibodies
Abstract
:1. Introduction
2. Materials and Methods
2.1. Serum Samples
2.2. Plaque Reduction Neutralization Test (PRNT)
2.3. Immunoassay System
2.4. Surrogate ELISAs
2.5. Statistical Analysis
3. Results
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Zhou, P.; Yang, X.-L.; Wang, X.-G.; Hu, B.; Zhang, L.; Zhang, W.; Si, H.-R.; Zhu, Y.; Li, B.; Huang, C.-L.; et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020, 579, 270–273. [Google Scholar] [CrossRef] [Green Version]
- Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R.; et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 2020, 382, 727–733. [Google Scholar] [CrossRef]
- WHO World Health Organization Coronavirus Disease (COVID-19) Dashboard. 2020. Available online: https://covid19.who.int/ (accessed on 16 March 2021).
- Huang, A.T.; Garcia-Carreras, B.; Hitchings, M.D.T.; Yang, B.; Katzelnick, L.C.; Rattigan, S.M.; Borgert, B.A.; Moreno, C.A.; Solomon, B.D.; Rodriguez-Barraquer, I.; et al. A systematic review of antibody mediated immunity to coronaviruses: Antibody kinetics, correlates of protection, and association of antibody responses with severity of disease. medRxiv 2020. [Google Scholar] [CrossRef]
- Dagan, N.; Barda, N.; Kepten, E.; Miron, O.; Perchik, S.; Katz, M.A.; Hernán, M.A.; Lipsitch, M.; Reis, B.; Balicer, R.D. BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting. N. Engl. J. Med. 2021, 384, 1412–1423. [Google Scholar] [CrossRef]
- U.S. Food and Drug Administration. EUA Authorized Serology Test Performance. Available online: https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-use-authorizations-medical-devices/eua-authorized-serology-test-performance (accessed on 18 March 2021).
- Fu, Y.; Pan, Y.; Li, Z.; Li, Y. The Utility of Specific Antibodies Against SARS-CoV-2 in Laboratory Diagnosis. Front. Microbiol. 2021, 11, 603058. [Google Scholar] [CrossRef]
- Kohmer, N.; Westhaus, S.; Rühl, C.; Ciesek, S.; Rabenau, H.F. Clinical performance of different SARS-CoV-2 IgG antibody tests. J. Med. Virol. 2020, 92, 2243–2247. [Google Scholar] [CrossRef]
- Okba, N.M.A.; Müller, M.A.; Li, W.; Wang, C.; GeurtsvanKessel, C.H.; Corman, V.M.; Lamers, M.M.; Sikkema, R.S.; De Bruin, E.; Chandler, F.D.; et al. Severe Acute Respiratory Syndrome Coronavirus 2−Specific Antibody Responses in Coronavirus Disease Patients. Emerg. Infect. Dis. 2020, 26, 1478–1488. [Google Scholar] [CrossRef] [PubMed]
- Infectious Disease Society of America. COVID-19 Guideline, Part 4: Serology. Available online: https://www.idsociety.org/practice-guideline/covid-19-guideline-serology (accessed on 18 March 2021).
- Nie, J.; Li, Q.; Wu, J.; Zhao, C.; Hao, H.; Liu, H.; Zhang, L.; Nie, L.; Qin, H.; Wang, M.; et al. Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2. Emerg. Microbes Infect. 2020, 9, 680–686. [Google Scholar] [CrossRef] [Green Version]
- Capcha, J.M.C.; Lambert, G.; Dykxhoorn, D.M.; Salerno, A.G.; Hare, J.M.; Whitt, M.A.; Pahwa, S.; Jayaweera, D.T.; Shehadeh, L.A. Generation of SARS-CoV-2 Spike Pseudotyped Virus for Viral Entry and Neutralization Assays: A 1-Week Protocol. Front. Cardiovasc. Med. 2021, 7, 618651. [Google Scholar] [CrossRef]
- Donofrio, G.; Franceschi, V.; Macchi, F.; Russo, L.; Rocci, A.; Marchica, V.; Costa, F.; Giuliani, N.; Ferrari, C.; Missale, G. A Simplified SARS-CoV-2 Pseudovirus Neutralization Assay. Vaccines 2021, 9, 389. [Google Scholar] [CrossRef] [PubMed]
- Muruato, A.E.; Fontes-Garfias, C.R.; Ren, P.; Garcia-Blanco, M.A.; Menachery, V.D.; Xie, X.; Shi, P.-Y. A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation. Nat. Commun. 2020, 11, 1–6. [Google Scholar] [CrossRef]
- Müller, K.; Girl, P.; von Buttlar, H.; Dobler, G.; Wölfel, R. Comparison of two commercial surrogate ELISAs to detect a neutralising antibody response to SARS-CoV-2. J. Virol. Methods 2021, 292, 114122. [Google Scholar] [CrossRef] [PubMed]
- Taylor, S.C.; Hurst, B.; Charlton, C.L.; Bailey, A.; Kanji, J.N.; McCarthy, M.K.; Morrison, T.E.; Huey, L.; Annen, K.; DomBourian, M.G.; et al. A New SARS-CoV-2 Dual-Purpose Serology Test: Highly Accurate Infection Tracing and Neutralizing Antibody Response Detection. J. Clin. Microbiol. 2021, 59. [Google Scholar] [CrossRef]
- The Medical Letter. An EUA for Bamlanivimab—A Monoclonal Antibody for COVID-19. JAMA 2021, 325, 880. [Google Scholar] [CrossRef] [PubMed]
- WHO. WHO/BS.2020.2403 Establishment of the WHO International Standard and Reference Panel for anti-SARS-CoV-2 Antibody. Available online: https://www.who.int/publications/m/item/WHO-BS-2020.2403 (accessed on 22 March 2021).
- Cohen, J. Weighted kappa: Nominal scale agreement provision for scaled disagreement or partial credit. Psychol. Bull. 1968, 70, 213–220. [Google Scholar] [CrossRef] [PubMed]
- Landis, J.R.; Koch, G.G. The Measurement of Observer Agreement for Categorical Data. Biometrics 1977, 33, 159–174. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bewley, K.R.; Coombes, N.S.; Gagnon, L.; McInroy, L.; Baker, N.; Shaik, I.; St-Jean, J.R.; St-Amant, N.; Buttigieg, K.R.; Humphries, H.E.; et al. Quantification of SARS-CoV-2 neutralizing antibody by wild-type plaque reduction neutralization, microneutralization and pseudotyped virus neutralization assays. Nat. Protoc. 2021, 1–33. [Google Scholar] [CrossRef]
- Matusali, G.; Colavita, F.; Lapa, D.; Meschi, S.; Bordi, L.; Piselli, P.; Gagliardini, R.; Corpolongo, A.; Nicastri, E.; Antinori, A.; et al. SARS-CoV-2 Serum Neutralization Assay: A Traditional Tool for a Brand-New Virus. Viruses 2021, 13, 655. [Google Scholar] [CrossRef]
- Shi, A.C.; Ren, P. SARS-CoV-2 serology testing: Progress and challenges. J. Immunol. Methods 2021, 494, 113060. [Google Scholar] [CrossRef]
- James, J.; Rhodes, S.; Ross, C.; Skinner, P.; Smith, S.; Shipley, R.; Warren, C.; Goharriz, H.; McElhinney, L.; Temperton, N.; et al. Comparison of Serological Assays for the Detection of SARS-CoV-2 Antibodies. Viruses 2021, 13, 713. [Google Scholar] [CrossRef]
- Tan, S.S.; Saw, S.; Chew, K.L.; Huak, C.Y.; Khoo, C.; Pajarillaga, A.; Wang, W.; Tambyah, P.; Ong, L.; Jureen, R.; et al. Head-to-head evaluation on diagnostic accuracies of six SARS-CoV-2 serological assays. Pathology 2020, 52, 770–777. [Google Scholar] [CrossRef] [PubMed]
- Valcourt, E.J.; Manguiat, K.; Robinson, A.; Chen, J.C.-Y.; Dimitrova, K.; Philipson, C.; Lamoureux, L.; McLachlan, E.; Schiffman, Z.; Drebot, M.A.; et al. Evaluation of a commercially-available surrogate virus neutralization test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Diagn. Microbiol. Infect. Dis. 2021, 99, 115294. [Google Scholar] [CrossRef] [PubMed]
- Nicholson, S.; Karapanagiotidis, T.; Khvorov, A.; Douros, C.; Mordant, F.; Bond, K.; Druce, J.; Williamson, D.A.; Purcell, D.; Lewin, S.R.; et al. Evaluation of six commercial SARS-CoV-2 Enzyme-Linked Immunosorbent assays for clinical testing and serosurveillance. medRxiv 2021. [Google Scholar] [CrossRef]
- Papenburg, J.; Cheng, M.P.; Corsini, R.; Caya, C.; Mendoza, E.; Manguiat, K.; Lindsay, L.R.; Wood, H.; Drebot, M.A.; Dibernardo, A.; et al. Evaluation of a Commercial Culture-free Neutralization Antibody Detection Kit for Severe Acute Respiratory Syn-drome-Related Coronavirus-2 and Comparison with an Anti-RBD ELISA Assay. medRxiv 2021. [Google Scholar] [CrossRef]
- Mariën, J.; Michiels, J.; Heyndrickx, L.; Nkuba-Ndaye, A.; Ceulemans, A.; Bartholomeeusen, K.; Madinga, J.; Mbala-Kingebeni, P.; Vanlerberghe, V.; Ahuka-Mundeke, S.; et al. Evaluation of a surrogate virus neutralization test for high-throughput serosurveillance of SARS-CoV-2. medRxiv 2021. [Google Scholar] [CrossRef]
- Legros, V.; Denolly, S.; Vogrig, M.; Boson, B.; Siret, E.; Rigaill, J.; Pillet, S.; Grattard, F.; Gonzalo, S.; Verhoeven, P.; et al. A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity. Cell. Mol. Immunol. 2021, 18, 318–327. [Google Scholar] [CrossRef]
- Glück, V.; Grobecker, S.; Tydykov, L.; Salzberger, B.; Glück, T.; Weidlich, T.; Bertok, M.; Gottwald, C.; Wenzel, J.J.; Gessner, A.; et al. SARS-CoV-2-directed antibodies persist for more than six months in a cohort with mild to moderate COVID-19. Infection 2021, 1–8. [Google Scholar] [CrossRef]
- Schlickeiser, S.; Schwarz, T.; Steiner, S.; Wittke, K.; Al Besher, N.; Meyer, O.; Kalus, U.; Pruß, A.; Kurth, F.; Zoller, T.; et al. Disease Severity, Fever, Age, and Sex Correlate With SARS-CoV-2 Neutralizing Antibody Responses. Front. Immunol. 2021, 11, 628971. [Google Scholar] [CrossRef] [PubMed]
- Arkhipova-Jenkins, I.; Helfand, M.; Armstrong, C.; Gean, E.; Anderson, J.; Paynter, R.A.; Mackey, K. Antibody Response After SARS-CoV-2 Infection and Implications for Immunity. Ann. Intern. Med. 2021. [Google Scholar] [CrossRef]
- Grupel, D.; Gazit, S.; Schreiber, L.; Nadler, V.; Wolf, T.; Lazar, R.; Supino-Rosin, L.; Perez, G.; Peretz, A.; Tov, A.B.; et al. Kinetics of SARS-CoV-2 anti-s IgG after BNT162b2 vaccination. medRxiv 2021. [Google Scholar] [CrossRef]
- Polack, F.P.; Thomas, S.J.; Kitchin, N.; Absalon, J.; Gurtman, A.; Lockhart, S.; Perez, J.L.; Marc, G.P.; Moreira, E.D.; Zerbini, C.; et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N. Engl. J. Med. 2020, 383, 2603–2615. [Google Scholar] [CrossRef] [PubMed]
- Lord, J.M. The effect of aging of the immune system on vaccination responses. Hum. Vaccines Immunother. 2013, 9, 1364–1367. [Google Scholar] [CrossRef] [Green Version]
- Müller, L.; Andrée, M.; Moskorz, W.; Drexler, I.; Walotka, L.; Grothmann, R.; Ptok, J.; Hillebrandt, J.; Ritchie, A.; Rabl, D.; et al. Age-dependent immune response to the Biontech/Pfizer BNT162b2 COVID-19 vaccination. Clin. Infect. Dis. 2021. [Google Scholar] [CrossRef]
- Bonifacius, A.; Tischer-Zimmermann, S.; Dragon, A.C.; Gussarow, D.; Vogel, A.; Krettek, U.; Gödecke, N.; Yilmaz, M.; Kraft, A.R.; Hoeper, M.M.; et al. COVID-19 immune signatures reveal stable antiviral T cell function despite declining humoral responses. Immunity 2021, 54, 340–354. [Google Scholar] [CrossRef]
- Li, Z.; Liu, J.; Deng, H.; Yang, X.; Wang, H.; Feng, X.; Zelinskyy, G.; Trilling, M.; Sutter, K.; Lu, M.; et al. SARS-CoV-2-specific T cell memory is long-lasting in the majority of convalsecent COVID-19 individuals. bioRixv 2020. [Google Scholar] [CrossRef]
- Yazıcı, M.K.; Koç, M.M.; Çetin, N.S.; Karaaslan, E.; Okay, G.; Durdu, B.; Sümbül, B.; Doymaz, M.Z. Discordance between Serum Neutralizing Antibody Titers and the Recovery from COVID-19. J. Immunol. 2020, 205, 2719–2725. [Google Scholar] [CrossRef] [PubMed]
- Dan, J.M.; Mateus, J.; Kato, Y.; Hastie, K.M.; Faliti, C.; Ramirez, S.I.; Frazier, A.; Esther, D.Y.; Grifoni, A.; Rawlings, S.A.; et al. Immunological memory to SARS-CoV-2 assessed for greater than six months after infection. bioRxiv 2020. [Google Scholar] [CrossRef]
PRNT | GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit | TECO® SARS-CoV-2 Neutralization Antibody Assay | Leinco COVID-19 ImmunoRank™ Neutralization MICRO-ELISA | SARS-CoV-2 IgG II Quant (Abbott) | ||
---|---|---|---|---|---|---|
Sensitivity (%) | all positive tested samples (titer ≥ 1:20) | n = 48 | 100% (48/48) (92.6–100% [95% CI]) | 100% (48/48) (92.6–100% [95% CI]) | 93.8 (45/48) (82.8–98.7% [95% CI]) | 100% (48/48) (92.6–100% [95% CI]) |
low level (titer 1:20–1:40) | n = 17 | 100% (17/17) (80.5–100% [95% CI]) | 100% (17/17) (80.5–100% [95% CI]) | 82.4% (14/17) (56.6–96.2% [95% CI]) | 100% (17/17) (80.5–100% [95% CI]) | |
high level (titer ≥ 1:80) | n = 31 | 100% (31/31) (88.8–100% [95% CI]) | 100% (31/31) (88.8–100% [95% CI]) | 100% (31/31) (88.8–100% [95% CI]) | 100% (31/31) (88.8–100% [95% CI]) | |
“borderline” (titer 1:10) | n = 7 | 5 × positive/ 2 × negative | 4 × positive/ 3 × negative | 1 × positive/ 6 × negative | 6 × positive/ 1 × negative | |
Specificity (%) | PRNT negative samples | n = 23 | 87% (20/23) (66.4–97.2% [95% CI]) | 78.3% (18/23) (56.3–92.5% [95% CI]) | 91.3% (21/23) (72–98.9% [95% CI]) | 73.9% (17 */23) (51.6–89.8% [95% CI]) |
GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit | TECO® SARS-CoV-2 Neutralization Antibody Assay | Leinco COVID-19 ImmunoRank™ Neutralization MICRO-ELISA | SARS-CoV-2 IgG II Quant (Abbott) | |
---|---|---|---|---|
weighted kappa | 0.9 | 0.830 | 0.841 | 0.793 |
standard error | 0.056 | 0.072 | 0.068 | 0.079 |
95% CI | 0.79–1 | 0.688–0.971 | 0.707–0.975 | 0.638–0.948 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Kohmer, N.; Rühl, C.; Ciesek, S.; Rabenau, H.F. Utility of Different Surrogate Enzyme-Linked Immunosorbent Assays (sELISAs) for Detection of SARS-CoV-2 Neutralizing Antibodies. J. Clin. Med. 2021, 10, 2128. https://doi.org/10.3390/jcm10102128
Kohmer N, Rühl C, Ciesek S, Rabenau HF. Utility of Different Surrogate Enzyme-Linked Immunosorbent Assays (sELISAs) for Detection of SARS-CoV-2 Neutralizing Antibodies. Journal of Clinical Medicine. 2021; 10(10):2128. https://doi.org/10.3390/jcm10102128
Chicago/Turabian StyleKohmer, Niko, Cornelia Rühl, Sandra Ciesek, and Holger F. Rabenau. 2021. "Utility of Different Surrogate Enzyme-Linked Immunosorbent Assays (sELISAs) for Detection of SARS-CoV-2 Neutralizing Antibodies" Journal of Clinical Medicine 10, no. 10: 2128. https://doi.org/10.3390/jcm10102128