Anti-Spike Protein Assays to Determine SARS-CoV-2 Antibody Levels: a Head-to-Head Comparison of Five Quantitative Assays

Perkmann, Thomas; Perkmann-Nagele, Nicole; Köller, Thomas; Mucher, Patrick; Radakovics, Astrid; Marculescu, Rodrig; Wolzt, Michael; Wagner, Oswald; Binder, Christoph J.; Haslacher, Helmuth

doi:10.1128/spectrum.00247-21

Cited by 161 publications

(157 citation statements)

References 43 publications

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“…The Elecsys Anti-SARS-CoV-2 S immunoassay was used for the quantitative determination of antibodies to the receptor-binding domain (RBD) of the viral spike (S) protein. 26,27 The quantitation range is between 0.4 and 2500.0□BAU/mL (binding antibody units per milliliter). A value greater than 0.8 BAU/mL was considered as positive.…”

Section: Methodsmentioning

confidence: 99%

Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

Bonelli

Mrak

Tobudic

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus–2 (SARS–CoV–2)–induced coronavirus disease 2019 (COVID–19) has led to exponentially rising mortality, particularly in immunosuppressed patients, who inadequately respond to conventional COVID–19 vaccination. In this blinded randomized clinical trial (EudraCT 2021–002348–57) we compare the efficacy and safety of an additional booster vaccination with a vector versus mRNA vaccine in non–seroconverted patients. We assigned 60 patients under rituximab treatment, who did not seroconvert after their primary mRNA vaccination with either BNT162b2 (Pfizer–BioNTech) or mRNA–1273 (Moderna), to receive a third dose, either using the same mRNA or the vector vaccine ChAdOx1 nCoV–19 (Oxford–AstraZeneca). Patients were stratified according to the presence of peripheral B–cells. The primary efficacy endpoint was the difference in the SARS–CoV–2 antibody seroconversion rate between vector (heterologous) and mRNA (homologous) vaccinated patients by week four. Key secondary endpoints included the overall seroconversion and cellular immune response; safety was assessed at weeks one and four. Seroconversion rates at week four were comparable between vector (6/27 patients, 22%) and mRNA (9/28, 32%) vaccine (p=0.6). Overall, 27% of patients seroconverted; specific T–cell responses were observed in 20/20 (100%) vector versus 13/16 (81%) mRNA vaccinated patients. Newly induced humoral and/or cellular responses occurred in 9/11 (82%) patients. No serious adverse events, related to immunization, were observed. This enhanced humoral and/or cellular immune response supports an additional booster vaccination in non–seroconverted patients irrespective of a heterologous or homologous vaccination regimen.

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Section: Methodsmentioning

confidence: 99%

Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

Bonelli

Mrak

Tobudic

et al. 2021

Preprint

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“…Both assays quantitate antibodies directed against the RBD domain of the SARS-CoV-2 spike protein and were referenced against the first WHO standard for SARS-CoV-2 antibodies, thus providing results in BAU/mL. We demonstrated in a previous study after vaccination with BNT162b that despite the standardization of SARS-CoV-2 antibody assays according to the first WHO standard for SARS-CoV-2 antibodies, the numerical values of different test systems are not interchangeable 27 . In the present work, we show for the first time that the problem of comparability is even more profound because the conversion of results may change dramatically with the time interval from vaccination.…”

Section: Discussionmentioning

confidence: 99%

“…Despite targeting the same antigen (RBD) and converting to the same units (BAU/mL) using the first WHO standard for SARS-CoV-2 antibodies, not even the relative increases in antibody levels turned out to be comparable. The limited comparability of serological assays after vaccination is not specific for the AstraZeneca vaccine, as it was also observed after immunization with Pfizer/BioNTech BNT162b2 27 .…”

Section: Discussionmentioning

confidence: 99%

“…These potential non-responders might be identified in a first step by determining the antibody levels after vaccination. Unfortunately, there is little scientific evidence on the real-life comparability of different commercially available quantitative test systems 27–29 .…”

Section: Introductionmentioning

confidence: 99%

“…We could previously show that referencing the WHO SARS-CoV-2 antibody standard by reporting standardized binding antibody units (BAU/mL) is insufficient for different test systems to provide numerically comparable results 27 . We demonstrated this in a strictly standardized study setting concerning the time of blood collection and the vaccine used: three weeks after the first dose of BNT162b2.…”

Section: Introductionmentioning

confidence: 99%

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The comparability of Anti-Spike SARS-CoV-2 antibody tests is time-dependent: a prospective observational study

Perkmann¹,

Mucher²,

Perkmann-Nagele³

et al. 2021

Preprint

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Objectives Various commercial anti-Spike SARS-CoV-2 antibody tests are used for studies and in clinical settings after vaccination. An international standard for SARS-CoV-2 antibodies has been established to achieve comparability of such tests, allowing conversions to BAU/ml. This study aimed to investigate the comparability of antibody tests regarding the timing of blood collection after vaccination. Methods For this prospective observational study, antibody levels of 50 participants with homologous AZD1222 vaccination were evaluated at 3 and 11 weeks after the first dose and 3 weeks after the second dose using two commercial anti-Spike binding antibody assays (Roche and Abbott) and a surrogate neutralization assay (sVNT). Results The correlation between Roche and Abbott changed significantly depending on the time point studied. Although 3 weeks after the first dose, Abbott provided values three times higher than Roche, 11 weeks after the first dose, the values for Roche were twice as high as for Abbott, and 3 weeks after the second dose even 5-6 times higher. Conclusions The comparability of quantitative anti-Spike SARS-CoV-2 antibody tests is highly dependent on the timing of blood collection after vaccination. Therefore, standardization of the timing of blood collection might be necessary for the comparability of different quantitative SARS-COV-2 antibody assays.

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Humoral Immune Response in Hematooncological Patients and Health Care Workers Who Received SARS-CoV-2 Vaccinations

et al. 2022

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IMPORTANCETo our knowledge, little is known about antibody development after SARS-CoV-2 vaccination in immunocompromised individuals, such as patients with cancer.OBJECTIVE To determine whether hematooncological patients develop anti-SARS-CoV-2 antibodies after vaccination. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study included 2 independent cohorts of patients who were treated for hematological and solid malignant tumors between October 2020 and May 2021, comprising 901 samples from 595 patients and 58 health care workers (HCWs). Serum samples were collected from patients who were treated at an academic center and a community hospital in a rural area and a control group of HCWs, all of whom received SARS-CoV-2 vaccination. MAIN OUTCOMES AND MEASURESTotal anti-SARS-CoV-2 nucleocapsid (anti-NC) and antispike protein (anti-S) antibodies were measured retrospectively. RESULTS In total, 595 patients (320 women [53.8%] and 275 men [46.2%]; median [range] age, 67 [19-96] years) and 58 HCWs (40 women [69.0%] and 18 men [31.0%]; median [range] age, 42 [24-60] years) were included. Previous SARS-CoV-2 infection was documented in 43 of 595 (7.2%), while anti-NC antibodies that suggested previous infections were observed in 49 of 573 evaluable patients (8.6%). In both cohorts, anti-S antibody levels were higher in fully vaccinated patients compared with patients who received 1 dose. After the first vaccination, patients with hematological cancer who received B cell-targeting agents had lower anti-S levels (median, 1.6 AU/mL; range: 0-17 244 AU/mL) than patients who received other therapies (median, 191.6 AU/mL; range, 0-40 000; P < .001) or patients with solid tumors (median, 246.4 AU/mL; range, 0-40 000 AU/mL; P < .001). Anti-S levels after the first vaccination differed according to ongoing antineoplastic treatment modalities, with the lowest median levels in patients who received chemotherapy alone (157.7 AU/mL; range, 0-40 000 AU/mL) or in combination with immunotherapy (118.7 AU/mL; range, 14.1-38 727 AU/mL) and the highest levels in patients with no ongoing antineoplastic treatment (median, 634.3 AU/mL; range, 0-40 000 AU/mL; P = .01). Antibody levels after full immunization were higher in HCWs (median, 2500 U/mL; range, 485-2500 U/mL) than in patients with cancer (median, 117.0 U/mL; range, 0-2500 U/mL; P < .001). CONCLUSIONS AND RELEVANCEIn this cohort study of patients with hematooncological diseases and a control group of HCWs, anti-SARS-CoV-2 antibodies after vaccination could be detected in patients with cancer. Lower antibody levels compared with HCWs and differences in seroconversion in specific subgroups underscore the need for further studies on SARS-CoV-2 vaccination in patients with hematooncological disease.

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Anti-Spike Protein Assays to Determine SARS-CoV-2 Antibody Levels: a Head-to-Head Comparison of Five Quantitative Assays

Abstract: Reliable quantification of the antibody response to SARS-CoV-2 is highly relevant, e.g., for identifying possible vaccine failure and estimating the time of protection. We compared the performance of five CE marked tests that quantify antibodies against the viral spike protein.

Cited by 161 publications

References 43 publications

Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

Additional heterologous versus homologous booster vaccination in immunosuppressed patients without SARS-CoV-2 antibody seroconversion after primary mRNA vaccination: a randomized controlled trial

The comparability of Anti-Spike SARS-CoV-2 antibody tests is time-dependent: a prospective observational study

Humoral Immune Response in Hematooncological Patients and Health Care Workers Who Received SARS-CoV-2 Vaccinations

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