Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay

Ester Lopez; Ebene R. Haycroft; Amy Adair; Francesca L. Mordant; Matthew T. O'Neill; Phillip Pymm; Samuel J. Redmond; Wen Shi Lee; Nicholas A. Gherardin; Adam K. Wheatley; Jennifer A. Juno; Kevin J. Selva; Samantha K. Davis; Samantha L. Grimley; Leigh Harty; Damian F.J. Purcell; Kanta Subbarao; Dale I. Godfrey; Stephen J. Kent; Wai Hong Tham; Amy W. Chung

doi:10.1172/jci.insight.150012

Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay

Ester Lopez, Ebene R. Haycroft, Amy Adair, Francesca L. Mordant, Matthew T. O'Neill, Phillip Pymm, Samuel J. Redmond, Wen Shi Lee, Nicholas A. Gherardin, Adam K. Wheatley, Jennifer A. Juno, Kevin J. Selva, Samantha K. Davis, Samantha L. Grimley, Leigh Harty, Damian F.J. Purcell, Kanta Subbarao, Dale I. Godfrey, Stephen J. Kent, Wai Hong ThamAmy W. Chung^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

Abstract

The SARS-CoV-2 receptor binding domain (RBD) is both the principal target of neutralizing antibodies and one of the most rapidly evolving domains, which can result in the emergence of immune escape mutations, limiting the effectiveness of vaccines and antibody therapeutics. To facilitate surveillance, we developed a rapid, high-throughput, multiplex assay able to assess the inhibitory response of antibodies to 24 RBD natural variants simultaneously. We demonstrate how this assay can be implemented as a rapid surrogate assay for functional cell-based serological methods to measure the SARS-CoV-2 neutralizing capacity of antibodies at the angiotensinconverting enzyme 2-RBD (ACE2-RBD) interface. We describe the enhanced affinity of RBD variants N439K, S477N, Q493L, S494P, and N501Y to the ACE2 receptor and demonstrate the ability of this assay to bridge a major gap for SARS-CoV-2 research, informing selection of complementary monoclonal antibody candidates and the rapid identification of immune escape to emerging RBD variants following vaccination or natural infection.

Original language	English
Article number	e150012
Journal	JCI insight
Volume	6
Issue number	16
DOIs	https://doi.org/10.1172/jci.insight.150012
Publication status	Published - 2021
Externally published	Yes

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Lopez, E., Haycroft, E. R., Adair, A., Mordant, F. L., O'Neill, M. T., Pymm, P., Redmond, S. J., Lee, W. S., Gherardin, N. A., Wheatley, A. K., Juno, J. A., Selva, K. J., Davis, S. K., Grimley, S. L., Harty, L., Purcell, D. F. J., Subbarao, K., Godfrey, D. I., Kent, S. J., ... Chung, A. W. (2021). Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay. JCI insight, 6(16), Article e150012. https://doi.org/10.1172/jci.insight.150012

@article{3af470bb04644dfbaaaf0cc14d316240,

title = "Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay",

abstract = "The SARS-CoV-2 receptor binding domain (RBD) is both the principal target of neutralizing antibodies and one of the most rapidly evolving domains, which can result in the emergence of immune escape mutations, limiting the effectiveness of vaccines and antibody therapeutics. To facilitate surveillance, we developed a rapid, high-throughput, multiplex assay able to assess the inhibitory response of antibodies to 24 RBD natural variants simultaneously. We demonstrate how this assay can be implemented as a rapid surrogate assay for functional cell-based serological methods to measure the SARS-CoV-2 neutralizing capacity of antibodies at the angiotensinconverting enzyme 2-RBD (ACE2-RBD) interface. We describe the enhanced affinity of RBD variants N439K, S477N, Q493L, S494P, and N501Y to the ACE2 receptor and demonstrate the ability of this assay to bridge a major gap for SARS-CoV-2 research, informing selection of complementary monoclonal antibody candidates and the rapid identification of immune escape to emerging RBD variants following vaccination or natural infection.",

author = "Ester Lopez and Haycroft, {Ebene R.} and Amy Adair and Mordant, {Francesca L.} and O'Neill, {Matthew T.} and Phillip Pymm and Redmond, {Samuel J.} and Lee, {Wen Shi} and Gherardin, {Nicholas A.} and Wheatley, {Adam K.} and Juno, {Jennifer A.} and Selva, {Kevin J.} and Davis, {Samantha K.} and Grimley, {Samantha L.} and Leigh Harty and Purcell, {Damian F.J.} and Kanta Subbarao and Godfrey, {Dale I.} and Kent, {Stephen J.} and Tham, {Wai Hong} and Chung, {Amy W.}",

note = "Publisher Copyright: {\textcopyright} 2021, Lopez et al.",

year = "2021",

doi = "10.1172/jci.insight.150012",

language = "English",

volume = "6",

journal = "JCI insight",

issn = "2379-3708",

publisher = "The American Society for Clinical Investigation",

number = "16",

}

Lopez, E, Haycroft, ER, Adair, A, Mordant, FL, O'Neill, MT, Pymm, P, Redmond, SJ, Lee, WS, Gherardin, NA, Wheatley, AK, Juno, JA, Selva, KJ, Davis, SK, Grimley, SL, Harty, L, Purcell, DFJ, Subbarao, K, Godfrey, DI, Kent, SJ, Tham, WH & Chung, AW 2021, 'Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay', JCI insight, vol. 6, no. 16, e150012. https://doi.org/10.1172/jci.insight.150012

TY - JOUR

T1 - Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay

AU - Lopez, Ester

AU - Haycroft, Ebene R.

AU - Adair, Amy

AU - Mordant, Francesca L.

AU - O'Neill, Matthew T.

AU - Pymm, Phillip

AU - Redmond, Samuel J.

AU - Lee, Wen Shi

AU - Gherardin, Nicholas A.

AU - Wheatley, Adam K.

AU - Juno, Jennifer A.

AU - Selva, Kevin J.

AU - Davis, Samantha K.

AU - Grimley, Samantha L.

AU - Harty, Leigh

AU - Purcell, Damian F.J.

AU - Subbarao, Kanta

AU - Godfrey, Dale I.

AU - Kent, Stephen J.

AU - Tham, Wai Hong

AU - Chung, Amy W.

PY - 2021

Y1 - 2021

N2 - The SARS-CoV-2 receptor binding domain (RBD) is both the principal target of neutralizing antibodies and one of the most rapidly evolving domains, which can result in the emergence of immune escape mutations, limiting the effectiveness of vaccines and antibody therapeutics. To facilitate surveillance, we developed a rapid, high-throughput, multiplex assay able to assess the inhibitory response of antibodies to 24 RBD natural variants simultaneously. We demonstrate how this assay can be implemented as a rapid surrogate assay for functional cell-based serological methods to measure the SARS-CoV-2 neutralizing capacity of antibodies at the angiotensinconverting enzyme 2-RBD (ACE2-RBD) interface. We describe the enhanced affinity of RBD variants N439K, S477N, Q493L, S494P, and N501Y to the ACE2 receptor and demonstrate the ability of this assay to bridge a major gap for SARS-CoV-2 research, informing selection of complementary monoclonal antibody candidates and the rapid identification of immune escape to emerging RBD variants following vaccination or natural infection.

AB - The SARS-CoV-2 receptor binding domain (RBD) is both the principal target of neutralizing antibodies and one of the most rapidly evolving domains, which can result in the emergence of immune escape mutations, limiting the effectiveness of vaccines and antibody therapeutics. To facilitate surveillance, we developed a rapid, high-throughput, multiplex assay able to assess the inhibitory response of antibodies to 24 RBD natural variants simultaneously. We demonstrate how this assay can be implemented as a rapid surrogate assay for functional cell-based serological methods to measure the SARS-CoV-2 neutralizing capacity of antibodies at the angiotensinconverting enzyme 2-RBD (ACE2-RBD) interface. We describe the enhanced affinity of RBD variants N439K, S477N, Q493L, S494P, and N501Y to the ACE2 receptor and demonstrate the ability of this assay to bridge a major gap for SARS-CoV-2 research, informing selection of complementary monoclonal antibody candidates and the rapid identification of immune escape to emerging RBD variants following vaccination or natural infection.

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DO - 10.1172/jci.insight.150012

M3 - Article

C2 - 34251356

AN - SCOPUS:85113387083

SN - 2379-3708

VL - 6

JO - JCI insight

JF - JCI insight

IS - 16

M1 - e150012

ER -

Simultaneous evaluation of antibodies that inhibit SARS-CoV-2 variants via multiplex assay

Abstract

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