Quantification of antibody avidities and accurate detection of SARS-CoV-2 antibodies in serum and saliva on plasmonic substrates

Liu, Tiancheng; Hsiung, Jessica; Zhao, Su; Kost, Jessica; Sreedhar, Deepika; Hanson, Carl V.; Olson, Kjerstie; Keare, Douglas; Chang, Shin Ting; Bliden, Kevin P.; Gurbel, Paul A.; Tantry, Udaya S.; Roche, John; Press, Cynthia; Boggs, John; Rodriguez-Soto, Jorge; Montoya, José G.; Tang, Meijie; Dai, Hongjie

doi:10.1038/s41551-020-00642-4

Cited by 88 publications

(88 citation statements)

References 55 publications

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“…The repeated findings on low avidity of IgG directed towards SARS‐CoV‐2 antigens, even several months after onset of clinical symptoms 11,13,14,19–21 ; are unique in viral serodiagnostics so far. Though Luo et al 12 stated that there was a strong correlation between avidity or IgG towards RBD and days after onset of symptoms, their findings are also supporting the findings on low avidity of IgG towards SARS‐CoV‐2 antigens, as the authors had used the very low concentration of 3 M urea in their study.…”

Section: Discussionmentioning

confidence: 99%

The challenge of avidity determination in SARS‐CoV‐2 serology

Bauer

Struck²,

Schreiner³

et al. 2021

Journal of Medical Virology

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The serological responses towards severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleoprotein, receptor-binding domain (RBD), and spike protein S1 are characterized by incomplete avidity maturation. Analysis with varying concentrations of urea allows to determine distinct differences in avidity maturation, though the total process remains at an unusually low level. Despite incomplete avidity maturation, this approach allows to define early and late stages of infection. It therefore can compensate for the recently described irregular kinetic patterns of immunoglobulin M and immunoglobulin G (IgG) directed towards SARS-CoV-2 antigens. The serological responses towards seasonal coronaviruses neither have a negative nor positive impact on SARS-CoV-2 serology in general. Avidity determination in combination with measurement of antibody titers and complexity of the immune response allows to clearly differentiate between IgG responses towards seasonal coronaviruses and SARS-CoV-2.Cross-reactions seem to occur with very low probability. They can be recognized by their pattern of response and through differential treatment with urea. As high avidity has been shown to be essential in several virus systems for the protective effect of neutralizing antibodies, it should be clarified whether high avidity of IgG directed towards RBD indicates protective immunity. If this is the case, monitoring of avidity should be part of the optimization of vaccination programs.

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Section: Discussionmentioning

confidence: 99%

The challenge of avidity determination in SARS‐CoV‐2 serology

Bauer

Struck²,

Schreiner³

et al. 2021

Journal of Medical Virology

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“… Strömer et al, 2020a , Strömer et al, 2020b also describe predominantly occurring low avidity IgG towards SARS-CoV-antigens, while using a prototype version as well as the final version of the same assay system as used by us. Liu et al 2020 reported that IgG towards S1 and RBD of SARS-CoV-2 showed avidity indices below 0.3 within the first 45 days after onset of disease, except for one serum with an avidity index of about 0.8 before day 10.…”

Section: Incomplete Avidity Maturation Of Igg After Natural Infectionmentioning

confidence: 96%

The potential significance of high avidity immunoglobulin G (IgG) for protective immunity towards SARS-CoV-2

Bauer

2021

International Journal of Infectious Diseases

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“…In a review of seven other newly reported COVID-19 antibody testing technologies, several were found to be semi-quantitative( Mairesse et al, 2020 ; Soleimani et al, 2021 ), while others have narrow dynamic range or lack clinically validation ( Table S2 ). ( Tan et al 2020 ; Shaw et al 2020 ; Roy et al 2020 ; Liu et al 2020 ; Dzimianski et al 2020 ) In general, we believe that the DNA-assisted nanopore assay can simultaneously quantify SARS-CoV-2 antibodies with higher accuracy and larger dynamic range, while correlating with results from the “gold standard diagnostic technology” ELISA.…”

Section: Discussionmentioning

confidence: 98%

Multiplex quantitative detection of SARS-CoV-2 specific IgG and IgM antibodies based on DNA-assisted nanopore sensing

Zhang

Wang

Wei

et al. 2021

Biosensors and Bioelectronics

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The coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread into a global pandemic. Early and accurate diagnosis and quarantine remain the most effective mitigation strategy. Although reverse transcriptase polymerase chain reaction (RT-qPCR) is the gold standard for COVID-19 diagnosis, recent studies suggest that nucleic acids were undetectable in a significant number of cases with clinical features of COVID-19. Serologic assays that detect human antibodies to SARS-CoV-2 serve as a complementary method to diagnose these cases, as well as to identify asymptomatic cases and qualified convalescent serum donors. However, commercially available enzyme-linked immunosorbent assays (ELISA) are laborious and non-quantitative, while point-of-care assays suffer from low detection accuracy. To provide a serologic assay with high performance and portability for potential point-of-care applications, we developed DNA-assisted nanopore sensing for quantification of SARS-CoV-2 related antibodies in human serum. Different DNA structures were used as detection reporters for multiplex quantification of immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies against the nucleocapsid protein of SARS-CoV-2 in serum specimens from patients with conformed or suspected infection. Comparing to a clinically used point-of-care assay and an ELISA assay, our technology can reliably quantify SARS-CoV-2 antibodies with higher accuracy, large dynamic range, and potential for assay automation.

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Quantification of antibody avidities and accurate detection of SARS-CoV-2 antibodies in serum and saliva on plasmonic substrates

Cited by 88 publications

References 55 publications

The challenge of avidity determination in SARS‐CoV‐2 serology

The challenge of avidity determination in SARS‐CoV‐2 serology

The potential significance of high avidity immunoglobulin G (IgG) for protective immunity towards SARS-CoV-2

Multiplex quantitative detection of SARS-CoV-2 specific IgG and IgM antibodies based on DNA-assisted nanopore sensing

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