TY - JOUR
T1 - Plasmonically Enhanced Ultrasensitive Epitope-Specific Serologic Assay for COVID-19
AU - Wang, Zheyu
AU - Morrissey, Jeremiah J.
AU - Liu, Lin
AU - Wang, Yixuan
AU - Zhou, Qingjun
AU - Naik, Rajesh R.
AU - Singamaneni, Srikanth
N1 - Funding Information:
Convalescent plasma samples utilized in this study were obtained from the Washington University School of Medicine’s COVID-19 biorepository, which is supported by: the Barnes-Jewish Hospital Foundation; the Siteman Cancer Center grant P30 CA091842 from the National Cancer Institute of the National Institutes of Health; and the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). This repository was developed and is maintained by Jane O’Halloran, MD, PhD; Charles Goss, PhD, and Phillip Mudd, MD, PhD. All patient samples used in this study were obtained under approval of IRB 202004097 from the Washington University Institutional Review Board. The content is solely the responsibility of the authors and does not necessarily represent the view of the NIH.
Funding Information:
The authors acknowledge support from National Science Foundation (CBET-2027145), National Cancer Institute-Innovative Molecular Analysis Technologies (R21CA236652), the National Cancer Institute (R01CA141521), and the Department of Anesthesiology of Washington University School of Medicine in St. Louis. The authors also thank Nano Research Facility (NRF) and Institute of Materials Science and Engineering (IMSE) at Washington University for providing access to electron microscopy facilities. The authors thank Dr. Qisheng Jiang and Dr. Jingyi Luan in Auragent Bioscience LLC for the preparation of plasmonic-fluor and application of dot blot assay.
Publisher Copyright:
© 2021 American Chemical Society
PY - 2022/1/18
Y1 - 2022/1/18
N2 - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread and resulted in the global pandemic of COVID-19. Although IgM/IgG serology assay has been widely used, with the entire spike or nucleocapsid antigens, they only indicate the presence or absence of antibodies against these proteins but are not specific to the neutralization antibodies, therefore providing only generic information about infection stage and possible future immune protection. Novel technologies enabling easy-to-use and sensitive detection of multiple specific antibodies simultaneously will facilitate precise diagnosis of infection stage, prediction of clinical outcomes, and evaluation of future immune protection upon viral exposure or vaccination. Here, we demonstrate a rapid and ultrasensitive quantification method for epitope-specific antibodies, including different isotypes and subclasses, in a multiplexed manner. Using an ultrabright fluorescent nanolabel, plasmonic-fluor, this novel assay can be completed in 20 min and more importantly, the limit of detection of the plasmon-enhanced immunoassay for SARS-CoV-2 antibodies is as much as 100-fold lower compared to the assays relying on enzymatic amplification of colorimetric signals. Using convalescent patient plasma, we demonstrate that this biodetection method reveals the patient-to-patient variability in immune response as evidenced by the variations in whole protein and epitope-specific antibodies. This cost-effective, rapid, and ultrasensitive plasmonically enhanced multiplexed epitope-specific serological assay has the potential to be broadly employed in the detection of specific antibodies, which may benefit the advanced epidemiology studies and enable improvement of the clinical outcomes and prediction of the future protection against the SARS-CoV-2.
AB - Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread and resulted in the global pandemic of COVID-19. Although IgM/IgG serology assay has been widely used, with the entire spike or nucleocapsid antigens, they only indicate the presence or absence of antibodies against these proteins but are not specific to the neutralization antibodies, therefore providing only generic information about infection stage and possible future immune protection. Novel technologies enabling easy-to-use and sensitive detection of multiple specific antibodies simultaneously will facilitate precise diagnosis of infection stage, prediction of clinical outcomes, and evaluation of future immune protection upon viral exposure or vaccination. Here, we demonstrate a rapid and ultrasensitive quantification method for epitope-specific antibodies, including different isotypes and subclasses, in a multiplexed manner. Using an ultrabright fluorescent nanolabel, plasmonic-fluor, this novel assay can be completed in 20 min and more importantly, the limit of detection of the plasmon-enhanced immunoassay for SARS-CoV-2 antibodies is as much as 100-fold lower compared to the assays relying on enzymatic amplification of colorimetric signals. Using convalescent patient plasma, we demonstrate that this biodetection method reveals the patient-to-patient variability in immune response as evidenced by the variations in whole protein and epitope-specific antibodies. This cost-effective, rapid, and ultrasensitive plasmonically enhanced multiplexed epitope-specific serological assay has the potential to be broadly employed in the detection of specific antibodies, which may benefit the advanced epidemiology studies and enable improvement of the clinical outcomes and prediction of the future protection against the SARS-CoV-2.
UR - http://www.scopus.com/inward/record.url?scp=85122281391&partnerID=8YFLogxK
U2 - 10.1021/acs.analchem.1c03676
DO - 10.1021/acs.analchem.1c03676
M3 - Article
C2 - 34935364
AN - SCOPUS:85122281391
SN - 0003-2700
VL - 94
SP - 909
EP - 917
JO - Analytical Chemistry
JF - Analytical Chemistry
IS - 2
ER -