Evaluation of a SARS-CoV-2 Surrogate Virus Neutralization Test for Detection of Antibody in Human, Canine, Cat, and Hamster Sera

Perera, Ranawaka A.P.M.; Ko, Ronald C.; Tsang, Owen Ty; Hui, David; Kwan, Mike Yat Wah; Brackman, Christopher J.; To, Esther M. W.; Yen, Hui-Ling; Leung, Kathy; Cheng, Samuel; Chan, Kin Ho; Chan, Ka‐Kui; Li, Ka-Chi; Saif, Linda J.; Barrs, Vanessa R.; Wu, Joseph T.; Sit, Thomas H. C.; Poon, Leo L M; Peiris, Malik

doi:10.1128/jcm.02504-20

Cited by 115 publications

(110 citation statements)

References 10 publications

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“… 5 , 7 In this 180-day longitudinal study of SARS-CoV-2 antibody dynamics, we focused specifically on functional neutralising antibodies using the operator-friendly surrogate virus neutralisation test assay platform, which has an excellent concordance with the live virus neutralisation test and has been successfully applied in multiple studies from different countries. 6 , 7 , 20 , 23 The surrogate virus neutralisation test offers advantages at the operational level for large numbers of samples and when repeated testing is required, as was the case for this study.…”

Section: Discussionmentioning

confidence: 88%

Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study

et al. 2021

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Background Studies have found different waning rates of neutralising antibodies compared with binding antibodies against SARS-CoV-2. The impact of neutralising antibody waning rate at the individual patient level on the longevity of immunity remains unknown. We aimed to investigate the peak levels and dynamics of neutralising antibody waning and IgG avidity maturation over time, and correlate this with clinical parameters, cytokines, and T-cell responses. Methods We did a longitudinal study of patients who had recovered from COVID-19 up to day 180 post-symptom onset by monitoring changes in neutralising antibody levels using a previously validated surrogate virus neutralisation test. Changes in antibody avidities and other immune markers at different convalescent stages were determined and correlated with clinical features. Using a machine learning algorithm, temporal change in neutralising antibody levels was classified into five groups and used to predict the longevity of neutralising antibody-mediated immunity. Findings We approached 517 patients for participation in the study, of whom 288 consented for outpatient follow-up and collection of serial blood samples. 164 patients were followed up and had adequate blood samples collected for analysis, with a total of 546 serum samples collected, including 128 blood samples taken up to 180 days post-symptom onset. We identified five distinctive patterns of neutralising antibody dynamics as follows: negative, individuals who did not, at our intervals of sampling, develop neutralising antibodies at the 30% inhibition level (19 [12%] of 164 patients); rapid waning, individuals who had varying levels of neutralising antibodies from around 20 days after symptom onset, but seroreverted in less than 180 days (44 [27%] of 164 patients); slow waning, individuals who remained neutralising antibody-positive at 180 days post-symptom onset (52 [29%] of 164 patients); persistent, although with varying peak neutralising antibody levels, these individuals had minimal neutralising antibody decay (52 [32%] of 164 patients); and delayed response, a small group that showed an unexpected increase of neutralising antibodies during late convalescence (at 90 or 180 days after symptom onset; three [2%] of 164 patients). Persistence of neutralising antibodies was associated with disease severity and sustained level of pro-inflammatory cytokines, chemokines, and growth factors. By contrast, T-cell responses were similar among the different neutralising antibody dynamics groups. On the basis of the different decay dynamics, we established a prediction algorithm that revealed a wide range of neutralising antibody longevity, varying from around 40 days to many decades. Interpretation Neutralising antibody response dynamics in patients who have recovered from COVID-19 vary greatly, and prediction of immune longevity can only be accurately determined at the individual level. Our findings emphas...

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Section: Discussionmentioning

confidence: 88%

Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study

et al. 2021

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“…The sVNT assays are well suited for a rapid prescreening of patient plasma to identify donors with high neutralization activity. In addition, sVNT kits are useful to analyzed animal sera from preclinical vaccine studies, because no adaptation of the assay is required ( Perera et al, 2020 ). A general limitation of these assays is that they are only able to detect neutralizing antibodies that function by blocking the interaction between the RBD and ACE2, although most neutralizing antibodies fulfill this requirement, single antibodies have been described that use other mechanisms for neutralization ( Wang et al, 2020 ), ( Wu et al, 2020b ).…”

Section: Discussionmentioning

confidence: 99%

Comparison of potency assays to assess SARS-CoV-2 neutralizing antibody capacity in COVID-19 convalescent plasma

Rhein

Scholz

Henß

et al. 2021

Journal of Virological Methods

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Highlights Transfusion of sera of convalescent patients is currently in clinical evaluations to treat COVID-19 patients. The level of neutralizing antibodies vary among convalescent patients and fast and simple methods to identify suitable plasma donations are needed. We compared three methods to determine the SARS-CoV-2 neutralizing activity of human convalescent plasma. An ELISA-based sVNT assay required the lowest biosafety level, was fast and sufficient to identify highly neutralizing plasma samples. Weakly neutralizing samples were more reliable detected by the more challenging lentiviral vector based assays or virus neutralization assays.

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“…A limitation of our study is that we only included a small panel of African samples ( n =55) to assess the specificity of the test and we cannot rule-out cross-reactivity at low titers on the cVNT, which we used as reference. However, there is overall agreement that the specificity of the sVNT is acceptably high (94-99% at sVNT 20 and 99-100% at sVNT 30 ) when evaluated on a panel containing challenging samples, including other coronaviruses or other acute infections (cross-reactivity against SARS-CoV-1 is noted)(8,10,13,14).…”

Section: Discussionmentioning

confidence: 96%

“…During serosurveillance studies, the test can also be run as an independent test to exclude cross-reactivity after the initial screening with a Luminex MIA assay. Furthermore, given that the test is both species and isotype independent, it could be used as a primary screening assay to detect reversed spillover or spillback events of SARS-CoV-2 from infected humans to wildlife populations or to find the natural reservoir of closely related sarbecoviruses in bats or other animal populations (8,9).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, detecting NAbs might be the only way to show past SARS-CoV-2 infections in particular wildlife populations for which secondary antibodies are unavailable (e.g. in populations of bat, pangolin or mink (8,9)). To overcome the difficulties of the cVNT, a surrogate viral neutralization test (sVNT) was recently developed that can be completed in 1-2 hours in a BSL2 laboratory and made commercially available by GenScript (10).…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of a surrogate virus neutralization test for high-throughput serosurveillance of SARS-CoV-2

Mariën

Míchiels

Heyndríckx

et al. 2021

Preprint

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High-throughput serological tests that can detect neutralizing antibodies against SARS-CoV-2 are desirable for serosurveillance and vaccine efficacy evaluation. Although the conventional neutralization test (cVNT) remains the gold standard to confirm the presence of neutralizing antibodies in sera, the test is too labour-intensive for massive screening programs and less reproducible as live virus and cell culture is involved. Here, we performed an independent evaluation of a commercially available surrogate virus neutralization test (sVNT, GenScript cPass) that can be done without biosafety level 3 containment in less than 2 hours. When using the cVNT and a Luminex multiplex immunoassay (MIA) as reference, the sVNT obtained a sensitivity of 94% (CI 90-96%) on a panel of 317 immune sera that were obtained from hospitalized and mild COVID-19 cases from Belgium and a sensitivity of 89% (CI 81-93%) on a panel of 184 healthcare workers from the Democratic Republic of Congo. We also found strong antibody titer correlations (rs>0.8) among the different techniques used. In conclusion, our evaluation suggests that the sVNT could be a powerful tool to monitor/detect neutralising antibodies in cohort and population studies. The technique could be especially useful for vaccine evaluation studies in sub-Saharan Africa where the basic infrastructure to perform cVNTs is lacking.

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Evaluation of a SARS-CoV-2 Surrogate Virus Neutralization Test for Detection of Antibody in Human, Canine, Cat, and Hamster Sera

Cited by 115 publications

References 10 publications

Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study

Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: a longitudinal study

Comparison of potency assays to assess SARS-CoV-2 neutralizing antibody capacity in COVID-19 convalescent plasma

Evaluation of a surrogate virus neutralization test for high-throughput serosurveillance of SARS-CoV-2

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