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

Autor: Cheedarla N; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Verkerke HP; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Potlapalli S; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., McLendon KB; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Patel A; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA., Frank F; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA., O'Sick WH; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Cheedarla S; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Baugh TJ; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Damhorst GL; Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA 30322, USA., Wu H; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Graciaa D; Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA 30322, USA., Hudaib F; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Alter DN; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Bryksin J; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Ortlund EA; Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA., Guarner J; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Auld S; Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA 30322, USA., Shah S; Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA 30322, USA.; Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA., Lam W; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA., Mattoon D; Quanterix Corporation, 900 Middlesex Turnpike, Billerica, MA 01821, USA., Johnson JM; Quanterix Corporation, 900 Middlesex Turnpike, Billerica, MA 01821, USA., Wilson DH; Quanterix Corporation, 900 Middlesex Turnpike, Billerica, MA 01821, USA., Dhodapkar MV; Department of Hematology/Medical Oncology, Emory University, Atlanta, GA, USA., Stowell SR; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA., Neish AS; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA., Roback JD; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Jazyk: angličtina
Zdroj: IScience [iScience] 2023 Oct 18; Vol. 26 (11), pp. 108256. Date of Electronic Publication: 2023 Oct 18 (Print Publication: 2023).
DOI: 10.1016/j.isci.2023.108256
Abstrakt: 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 pseudovirus 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.
Competing Interests: N.C., H.V., S.P., K.B.M., W.H.Os., H.W., A.S.N., and J.D.R. are co-inventors of BoAb assay technology. Emory University filed a patent on this technology.
(© 2023 The Authors.)
Databáze: MEDLINE