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Principal Investigator: Chao Wang
Organization: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
Fiscal Year: 2022
Award: $229,011
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary/Abstract
As of mid June 2021, the new coronavirus disease (COVID-19), caused by SARS-CoV-2 virus, has infected
~180 million people and causing ~3.8 million deaths globally. There are more than 34 million confirmed cases
and ~620,000 deaths in the U.S alone. The fast transmission, asymptotic infection in some individuals, currently
still limited supplies of vaccines in many countries, and constant virus mutation have made COVID-19 an
unprecedented global threat to human health and economics. Neutralizing antibodies (nAbs) recognize SARS-
CoV-2’s spike protein and block cellular entry, acting as the first responders in the immune system towards
pathogen clearance. Evaluating the effectiveness of nAbs against viral pathogens is important in understanding
the level and duration of sterilizing immunity after natural infection or following vaccination, particularly given the
rise of novel variants with vaccine escape potential. However, many of the available neutralizing assays used to
assess nAb function involve propagation of viruses and thus require such assays be conducted in a biosafety
level 3 (BSL3) lab settings, which, unfortunately, is unavailable to many researchers or clinicians. In addition,
clinical laboratory-based antibody tests measure the total Ab level responding to SARS-CoV-2 antigens, without
functionally evaluating pathogen-bound Abs and therefore cannot predict neutralizing activity. To bridge these
technological gaps, we propose a multidisciplinary research plan to address the fundamental challenges in low-
cost, high-throughput, fast, simple, and quantitative assay format in studying COVID-19 immune response. The
investigators at ASU with complementary expertise in nanosensor design, antibody characterization, and
coronaviruses will collaboratively develop a new and high-reward research strategy to establish a metal
nanoparticle (MNP)-based nAb assay platform. This platform presents a few key features distinguishing it from
previous technologies. First, the MNP assays are quantitative and accurate, with an expected dynamic range of
3 to 4 logs and a detection limit in the picomolar range. Further, this assay can be implemented in a rapid
detection format without any washing steps, thus significantly simplifying its operation, reducing assay time to a
few minutes, and making it feasible for mass-testing. Importantly, the assay is capable of detecting virus variants
by targeted binding to the epitopes on the spike protein that are sensitive to mutations. Additionally, the readout
can be performed in a well plate compatible with high-throughput screening with added portable electronic
components, making the system automated in both detection and data analysis. We envision the employment
of this rapid and quantitative nAb assay will also help timely determine the potential best uses of convalescent
plasma and antibody treatment with future emerging novel viruses. Its low cost, simple operation, and automation
capability are also very useful in longitudinal studies of the immune response related to COVID-19 infection,
vaccination, and potential viral escape due to mutations. The nAb sensing can also be used for large-population
sero-surveillance in determining the level of population-based immunity (herd immunity) against any virus strains.
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