Comparison of two commercial surrogate ELISAs to detect a neutralising antibody response to SARS-CoV-2

Müller, Katharina; Girl, Philipp; Buttlar, Heiner von; Dobler, Gerhard; Wölfel, Roman

doi:10.1016/j.jviromet.2021.114122

Cited by 33 publications

(34 citation statements)

References 24 publications

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“…Using the DiaSorin “Liaison SARS-CoV-2 S1/S2 IgG assay” ( Krüttgen et al, 2021 ) and a surrogate virus neutralization assay (“TECO SARS-CoV-2 Neutralization Antibody Assay”, TECOmedical) ( Müller et al, 2021 ), we confirmed that all vaccinees (18/18) in our study had successfully mounted humoral immune responses after mRNA-1273 vaccination (data not shown). We also tested our vaccinees for anti-Nucleocapsid IgG (“recomWell SARS-CoV-2 IgG ELISA” from Microgen) which is a marker for past covid-infections.…”

Section: Resultssupporting

confidence: 64%

Evaluation of the QuantiFERON SARS-CoV-2 interferon-ɣ release assay in mRNA-1273 vaccinated health care workers

Krüttgen

Klingel

Haase

et al. 2021

Journal of Virological Methods

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Current studies focus on cellular and humoral immunity induced by novel SARS-CoV-2 vaccines. Non-responders to vaccinations are not uncommonly encountered in clinical medicine (e.g. in the field of hepatitis B). Whereas vaccine-induced humoral immunity against SARS-CoV-2 is compromised by emerging Variants of Concern (VOCs), cellular immunity against SARS-CoV-2 is emerging as resilient against VOCs. Thus commercially available test kits for diagnostic laboratories designed to evaluate cellular immune responses to SARS-CoV-2 are urgently needed. Here we evaluated the novel QuantiFERON SARS-CoV-2 assay (Qiagen) measuring INF-ɣ release induced by two spike-derived peptide pools (Ag1 and Ag2) in a cohort of health care workers vaccinated with the mRNA-1273 vaccine and confirmed humoral response. Our study indicates the usefulness of this novel assay for routine laboratories to evaluate cellular immunity against SARS-CoV-2 in response to mRNA-1273 vaccination.

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Section: Resultssupporting

confidence: 64%

Evaluation of the QuantiFERON SARS-CoV-2 interferon-ɣ release assay in mRNA-1273 vaccinated health care workers

Krüttgen

Klingel

Haase

et al. 2021

Journal of Virological Methods

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“…This result differs from the results of a recently published study by Müller K et. al., in which only 68.7% (158/230) of these IgG positive samples were also positive in NTs [17]. This paper uses ELISA method to detect COVID-19 antibody, which is different from chemiluminescence method used in our paper.…”

Section: Discussionmentioning

confidence: 97%

Studies on the level of neutralizing antibodies produced by inactivated COVID-19 vaccines in the real world

Zhang

Jia

et al. 2021

Preprint

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BackgroundAlthough effective vaccines have been developed against COVID-19, the level of neutralizing antibodies (Nabs) induced after vaccination in the real world is still unknown. To evaluate the level and persistence of NAbs induced by two inactivated COVID-19 vaccines in China.Methods and findingsSerum samples were collected from 1,335 people aged 18 and over who were vaccinated with COVID-19 inactivated vaccine in Peking University People’s Hospital from January 19 to June 23, 2021, for detection of COVID-19 antibodies. The WHO standard of SARS-CoV-2 NAbs was detected. The coefficients of variation between the detection results and the true values of the NAbs detected by the WHO standard were all lower than the WHO international standard 3% after the dilution of the original and the dilution of the theoretical concentrations of 500 IU/mL, 250 IU/mL, 125 IU/mL, 72.5 IU/mL, 36.25 IU/mL and 18.125 IU/mL. On day 11-70, the positive rate of NAbs against COVID-19 was 82% to 100%; From day 71 to 332, the positive rate of NAbs decreased to 27%. The level of NAbs was significantly higher at 3-8 Weeks than at 0-3 Weeks. There was a high linear correlation between NAbs and IgG antibodies in 1335 vaccinated patients. NAbs levels were decreased in 31 of 38 people (81.6%) at two time points after the second dose of vaccine. There was no significant difference in age between the group with increased and decreased neutralizing antibody levels (χ2 =-0.034, P>0.05). The positive rate of NAbs in the two-dose vaccine group (77.3%) was significantly higher than that in the one-dose group (18.1%), with statistical difference (χ2=312.590, P<0.001). A total of 206 people who were 11-70 days after receiving the second dose were tested and divided into three groups: 18-40 years old, 41-60 years old and >60 years old. The positive rates of NAbs in three groups (18-40 years old, 41-60 years old and >60 years old) were 95.14%, 78.43% and 81.8%, respectively. The positive rate of NAbs was significantly higher in 18-40 years old than in 41-60 years old (χ2=12.547, P <0.01). The titer of NAbs in 18-40 years old group was significantly higher than that in 41-60 years old group (t=-0.222, P <0.01). The positive rate of NAbs in male group (89.32%) was lower than in female (91.26%), but there was no significant difference (χ2=0.222, P >0.05).ConclusionsThe positive rate of NAbs was the highest from 10 to 70 days after the second dose of vaccine, and the positive rate gradually decreased as time went by. There was a high linear correlation between COVID-19 NAbs and IgM/IgG antibodies in vaccinators, suggesting that in cases where NAbs cannot be detected, IgM/IgG antibodies can be detected instead. The level of NAbs produced after vaccination was affected by age, but not by gender. The highest levels of NAbs were produced between shots 21 to 56 days apart, suggesting that 21 to 56 days between shots is suitable for vaccination.Author summaryWhy was this study done?At present, the inactivated vaccines that have been approved to market in China have passed clinical trials to prove their effectiveness and safety. But the level of neutralizing antibodies induced by vaccination in the real world remains unclear.Serological testing for neutralizing antibodies against COVID-19 is important for assessing vaccine and treatment responses and comparing multiple drug candidates. We assessed the levels of neutralizing antibodies produced in populations receiving inactivated vaccines and assessed the persistence of these vaccines in producing COVID-19 neutralizing antibodies in healthy adults.What did the researchers do and find?We collected serum samples from 1,335 people aged 18 and above who had received COVID-19 vaccine in Peking University People’s Hospital, and divided them into two groups according to one dose of inactivated vaccine and two doses of inactivated vaccine.Our study found that the positive rate of NAbs was 66.2% in adults who received one or two doses of inactivated vaccine and 77.3% in adults who received two doses of inactivated vaccine in the real world.From 11 to 70 days after the second dose of vaccine, the positive rate of neutralizing antibodies against COVID-19 was 82-100%; On days 71-332, the positive rate of neutralizing antibodies decreased to 27%.The titer and the positive rate of NAbs in 18-40 years old group were significantly higher than that in 41-60 years old group.What do these findings mean?What is novel is we observed that in the real world, the positive rate of neutralization antibody was the highest at 10 to 70 days after the second vaccination, and with the extension of the vaccination time, the positive rate of antibody gradually decreased. Therefore, we recommend that the third dose of vaccine be administered at day 61 to day 70 for COVID-19 neutralizing antibodies levels.We observed that there was a high linear correlation between COVID-19 neutralization antibodies and COVID-19 IgM/IgG antibodies in vaccinators, suggesting that in cases where NAbs cannot be detected, COVID-19 IgM/IgG antibodies can be detected instead.In our manuscript, we found that the titer and positive rate of neutralizing antibodies in 18-40 years old group were higher than those in 41-60 years old group. The level of neutralizing antibodies produced after vaccination was affected by age, but not by gender.We also observed that the highest levels of NAbs were produced between shots 21 to 35 days apart, suggesting that 21 to 35 days between shots is suitable for vaccination.

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“…Of the surrogate ELISAs examined in our study, the GenScript assay demonstrated the highest sensitivity of 100% and a specificity of 87%, which is comparable to data from other studies. In the literature, also, testing clinical specimens and when the PRNT is used as the reference method, sensitivity ranges from 77 to 100% and specificity ranges from 69.5 to 100% [ 15 , 26 , 27 , 28 ]. When serum follow-up samples taken >14 days after rRT-PCR positivity were analyzed, the GenScript assay demonstrated a sensitivity of 97.3% and a specificity of 99.4% [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…These assays work according to the principle of competitive binding: anti-SARS-CoV-2 neutralizing antibodies block an enzyme-labeled S-RBD protein from binding its natural ligand, the angiotensin-converting enzyme 2 (ACE2), pre-coated on a microtiter plate. Surrogate ELISAs are high-throughput capable and can be performed under standard laboratory safety conditions [ 15 , 16 ]. However, there are limited data on their performance when testing specimens of individuals with past SARS-CoV-2 infection or follow-up samples of SARS-CoV-2 vaccinated individuals and especially how they compare to the PRNT.…”

Section: Introductionmentioning

confidence: 99%

Utility of Different Surrogate Enzyme-Linked Immunosorbent Assays (sELISAs) for Detection of SARS-CoV-2 Neutralizing Antibodies

Kohmer

Rühl

Ciesek

et al. 2021

JCM

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The plaque reduction neutralization test (PRNT) is a preferred method for the detection of functional, SARS-CoV-2 specific neutralizing antibodies from serum samples. Alternatively, surrogate enzyme-linked immunosorbent assays (ELISAs) using ACE2 as the target structure for the detection of neutralization-competent antibodies have been developed. They are capable of high throughput, have a short turnaround time, and can be performed under standard laboratory safety conditions. However, there are very limited data on their clinical performance and how they compare to the PRNT. We evaluated three surrogate immunoassays (GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit (GenScript Biotech, Piscataway Township, NJ, USA), the TECO® SARS-CoV-2 Neutralization Antibody Assay (TECOmedical AG, Sissach, Switzerland), and the Leinco COVID-19 ImmunoRank™ Neutralization MICRO-ELISA (Leinco Technologies, Fenton, MO, USA)) and one automated quantitative SARS-CoV-2 Spike protein-based IgG antibody assay (Abbott GmbH, Wiesbaden, Germany) by testing 78 clinical samples, including several follow-up samples of six BNT162b2 (BioNTech/Pfizer, Mainz, Germany/New York, NY, USA) vaccinated individuals. Using the PRNT as a reference method, the overall sensitivity of the examined assays ranged from 93.8 to 100% and specificity ranged from 73.9 to 91.3%. Weighted kappa demonstrated a substantial to almost perfect agreement. The findings of our study allow these assays to be considered when a PRNT is not available. However, the latter still should be the preferred choice. For optimal clinical performance, the cut-off value of the TECO assay should be individually adapted.

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Comparison of two commercial surrogate ELISAs to detect a neutralising antibody response to SARS-CoV-2

Cited by 33 publications

References 24 publications

Evaluation of the QuantiFERON SARS-CoV-2 interferon-ɣ release assay in mRNA-1273 vaccinated health care workers

Evaluation of the QuantiFERON SARS-CoV-2 interferon-ɣ release assay in mRNA-1273 vaccinated health care workers

Studies on the level of neutralizing antibodies produced by inactivated COVID-19 vaccines in the real world

Utility of Different Surrogate Enzyme-Linked Immunosorbent Assays (sELISAs) for Detection of SARS-CoV-2 Neutralizing Antibodies

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