Rapid, high throughput, automated detection of SARS-CoV-2 neutralizing antibodies against Wuhan-WT, delta and omicron BA1, BA2 spike trimers

被引：3

作者：

Cheedarla, Narayanaiah ^{[1
]}

Verkerke, Hans P. ^{[1
,2
]}

Potlapalli, Sindhu ^{[1
]}

McLendon, Kaleb Benjamin ^{[1
]}

Patel, Anamika ^{[3
]}

Frank, Filipp ^{[3
]}

O'Sick, William Henry ^{[1
]}

Cheedarla, Suneethamma ^{[1
]}

Baugh, Tyler Jon ^{[1
]}

Damhorst, Gregory L. ^{[4
]}

Wu, Huixia ^{[1
]}

Graciaa, Daniel ^{[4
]}

Hudaib, Fuad ^{[1
]}

Alter, David N. ^{[1
]}

Bryksin, Janetta ^{[1
]}

Ortlund, Eric A. ^{[3
]}

Guarner, Jeanette ^{[1
]}

Auld, Sara ^{[4
]}

Shah, Sarita ^{[4
,5
]}

Lam, Wilbur ^{[6
,7
]}

Mattoon, Dawn ^{[8
]}

Johnson, Joseph M. ^{[8
]}

Wilson, David H. ^{[8
]}

Dhodapkar, Madhav V. ^{[9
]}

Stowell, Sean R. ^{[2
]}

Neish, Andrew S. ^{[1
]}

Roback, John D. ^{[1
]}

机构：

[1] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA

[2] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[3] Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA

[4] Emory Univ, Dept Med, Div Infect Dis, Atlanta, GA 30322 USA

[5] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA

[6] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA USA

[7] Emory Univ, Atlanta, GA USA

[8] Quanterix Corp, 900 Middlesex Turnpike, Billerica, MA 01821 USA

[9] Emory Univ, Dept Hematol Med Oncol, Atlanta, GA USA

来源：

ISCIENCE | 2023年 / 26卷 / 11期

基金：

美国国家卫生研究院;

关键词：

Biochemical assay; Diagnostics; Virology;

D O I：

10.1016/j.isci.2023.108256

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor-and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of human angiotensin converting enzyme 2 (hACE-2) binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using Wuhan-WT (vaccine strain), delta (B.1.167.2), omicron BA1 and BA2 variant viral strains showed strong correlation with cell-based pseudo virus neutralization activity (PNA) and live-virus neutralization activity. Importantly, we were able to detect similar patterns of delta and omicron variant resistance to neutralization in samples with paired vaccine strain and delta variant BoAb measurements. Finally, we screened clinical samples from patients with or without evidence of SARS-CoV-2 exposure by a single-dilution screening version of our assays, finding significant nAb activity only in exposed individuals. Importantly, this completely automated assay can be performed in 4 h to measure neutralizing antibody titers for 16 samples over 8 serial dilutions or, 128 samples at a single dilution with replicates. In principle, these assays offer a rapid, robust, and scalable alternative to time-, skill-, and cost-intensive standard methods for measuring SARS-CoV-2 nAb levels.

引用

页数：15

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