Thermodynamically coupled biosensors for detecting neutralizing antibodies against SARS-CoV-2 variants

Zhang, Jason Z.; Yeh, Hsien‐Wei; Walls, Alexandra C.; Wicky, Basile I. M.; Sprouse, Kaitlin R.; VanBlargan, Laura A.; Treger, Rebecca S.; Quijano‐Rubio, Alfredo; Pham, Minh N.; Kraft, John C.; Haydon, Ian C; Yang, Wei; DeWitt, Michelle; Bowen, John E.; Chow, Cameron M.; Carter, Lauren; Ravichandran, Rashmi; Wener, Mark H.; Stewart, Lance; Veesler, David; Diamond, Michael S.; Greninger, Alexander L.; Koelle, David M.; Baker, David

doi:10.1038/s41587-022-01280-8

Cited by 25 publications

(18 citation statements)

References 29 publications

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“…Recently, the LOCKR platform used a binding module grafted into a caging structure that allows for enzyme reconstitution triggered by analyte binding (Figure S1c). − In this system, the binding module serves as the “lock” for a caging structure that masks one half of the split luciferase. The analyte serves as a “key” that opens the cage and allows the association of the other half of the split luciferase, which is added as a second component.…”

Section: Introductionmentioning

confidence: 99%

A Single-Component Luminescent Biosensor for the SARS-CoV-2 Spike Protein

et al. 2022

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Many existing protein detection strategies depend on highly functionalized antibody reagents. A simpler and easier to produce class of detection reagent is highly desirable. We designed a single-component, recombinant, luminescent biosensor that can be expressed in laboratory strains of Escherichia coli and Saccharomyces cerevisiae. This biosensor is deployed in multiple homogeneous and immobilized assay formats to detect recombinant SARS-CoV-2 spike antigen and cultured virus. The chemiluminescent signal generated facilitates detection by an unaugmented cell phone camera. Binding-activated tandem split-enzyme (BAT) biosensors may serve as a useful template for diagnostics and reagents that detect SARS-CoV-2 antigens and other proteins of interest.

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Section: Introductionmentioning

confidence: 99%

A Single-Component Luminescent Biosensor for the SARS-CoV-2 Spike Protein

et al. 2022

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“…Cohort and TRB repertoire sequencing Bulk TCR beta (TRB) repertoires from 259 peripheral blood mononuclear cells (PBMC) specimensspanning convalescence through booster vaccination -were sequenced from 54 persons reporting PCRdocumented COVID-19 between April-August 2020, when the SARS-CoV-2 ancestral-like D614G strain prevailed 21 . The cohort has been described [22][23][24][25] . The 18 hospitalized and 36 non-hospitalized SARS-CoV-2-infected persons had serial blood sampling through mRNA vaccination (demographics in Supplemental Data Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…A pre-vaccine TRB repertoire (at visit E01) was obtained from 34 participants immediately before vaccination, a median of 369 days (IQR 333-390) after symptom onset. Most participants had a TRB repertoire 2.5 to 4 weeks after mRNA dose 1 and prior to dose 2 at visit E02 (N = 52, median 19.5 days post dose 1, IQR [15][16][17][18][19][20][21][22][23][24] and after dose 2 at E03 (N = 53, median 24 days post dose 2, IQR 20-28). Forty-four persons had an mRNA booster (third dose) a median of 259 (IQR 230-283) days after primary vaccination, and a TRB repertoire at E05 (median 41.5 days after booster, IQR 26-69).…”

Section: Resultsmentioning

confidence: 99%

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CD8+ T cell clonotypes from prior SARS-CoV-2 infection predominate during the cellular immune response to mRNA vaccination

Ford¹,

Mayer-Blackwell²,

Jing³

et al. 2022

Preprint

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Almost three years into the SARS-CoV-2 pandemic, hybrid immunity is highly prevalent worldwide and more protective than vaccination or prior infection alone. Given emerging resistance of variant strains to neutralizing antibodies (nAb), it is likely that T cells contribute to this protection. To understand how sequential SARS-CoV-2 infection and mRNA-vectored SARS-CoV-2 spike (S) vaccines affect T cell clonotype-level expansion kinetics, we identified and cross-referenced TCR sequences from thousands of S-reactive single cells against deeply sequenced peripheral blood TCR repertoires longitudinally collected from persons during COVID-19 convalescence through booster vaccination. Successive vaccinations recalled memory T cells and elicited antigen-specific T cell clonotypes not detected after infection. Vaccine-related recruitment of novel clonotypes and the expansion of S-specific clones were most strongly observed for CD8+ T cells. Severe COVID-19 illness was associated with a more diverse CD4+ T cell response to SARS-CoV-2 both prior to and after mRNA vaccination, suggesting imprinting of CD4+ T cells by severe infection. TCR sequence similarity search algorithms revealed myriad public TCR clusters correlating with human leukocyte antigen (HLA) alleles. Selected TCRs from distinct clusters functionally recognized S in the predicted HLA context, with fine viral peptide requirements differing between TCRs. Most subjects tested had S-specific T cells in the nasal mucosa after a 3rd mRNA vaccine dose. The blood and nasal T cell responses to vaccination revealed by clonal tracking were more heterogeneous than nAb boosts. Analysis of bulk and single cell TCR sequences reveals T cell kinetics and diversity at the clonotype level, without requiring prior knowledge of T cell epitopes or HLA restriction, providing a roadmap for rapid assessment of T cell responses to emerging pathogens.

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“…Biosensor development for SARS-CoV-2 diagnostic is a challenge to researchers. Biosensors with transducers have demonstrated superior specificity and sensitivity to other diagnostic techniques, but only under controlled laboratory conditions (known virus concentration in buffered solution or hyperimmune sera produced in laboratory animals) [ 13 , 14 ]. Most of these devices show poor performance when tested in clinical practice due to contaminants abundant in enzymes in pharyngeal swabs, mucus, and cellular detritus, among others.…”

Section: Introductionmentioning

confidence: 99%

Challenges in the Detection of SARS-CoV-2: Evolution of the Lateral Flow Immunoassay as a Valuable Tool for Viral Diagnosis

et al. 2022

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SARS-CoV-2 is an emerging infectious disease of zoonotic origin that caused the coronavirus disease in late 2019 and triggered a pandemic that has severely affected human health and caused millions of deaths. Early and massive diagnosis of SARS-CoV-2 infected patients is the key to preventing the spread of the virus and controlling the outbreak. Lateral flow immunoassays (LFIA) are the simplest biosensors. These devices are clinical diagnostic tools that can detect various analytes, including viruses and antibodies, with high sensitivity and specificity. This review summarizes the advantages, limitations, and evolution of LFIA during the SARS-CoV-2 pandemic and the challenges of improving these diagnostic devices.

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Thermodynamically coupled biosensors for detecting neutralizing antibodies against SARS-CoV-2 variants

Cited by 25 publications

References 29 publications

A Single-Component Luminescent Biosensor for the SARS-CoV-2 Spike Protein

A Single-Component Luminescent Biosensor for the SARS-CoV-2 Spike Protein

CD8+ T cell clonotypes from prior SARS-CoV-2 infection predominate during the cellular immune response to mRNA vaccination

Challenges in the Detection of SARS-CoV-2: Evolution of the Lateral Flow Immunoassay as a Valuable Tool for Viral Diagnosis

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