Epitope-Functionalized Gold Nanoparticles for Rapid and Selective Detection of SARS-CoV-2 IgG Antibodies

Abstract

Rapid and inexpensive immunodiagnostic assays to monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroconversion are essential for conducting large-scale COVID-19 epidemiological surveillance and profiling humoral responses against SARS-CoV-2 infections or immunizations. Herein, a colorimetic serological assay to detect SARS-CoV-2 IgGs in patients’ plasma was developed using short antigenic epitopes conjugated to gold nanoparticles (AuNPs). Four immunodominant linear B-cell epitopes, located on the spike (S) and nucleocapsid (N) proteins of SARS-CoV-2, were characterized for their IgG binding affinity and used as highly specific biological motifs on the nanoparticle to recognize target antibodies. Specific bivalent binding between SARS-CoV-2 antibodies and epitope-functionalized AuNPs trigger nanoparticle aggregation, which manifests as a distinct optical transition in the AuNPs’ plasmon characteristics within 30 min of antibody introduction. Co-immobilization of two epitopes improved the assay sensitivity relative to single-epitope AuNPs with a limit of detection of 3.2 nM, commensurate with IgG levels in convalescent COVID-19-infected patients. A passivation strategy was further pursued to preserve the sensing response in human plasma medium. When tested against 35 clinical plasma samples of varying illness severity, the optimized nanosensor assay can successfully identify SARS-CoV-2 infection with 100% specificity and 83% sensitivity. As the epitopes are conserved within the circulating COVID-19 variants, the proposed platform holds great potential to serve as a cost-effective and highly specific alternative to classical immunoassays employing recombinant viral proteins. These epitope-enabled nanosensors further expand the serodiagnostic toolbox for COVID-19 epidemiological study, humoral response monitoring, or vaccine efficiency assessment.

Single Virus Detection on Silicon Photonic Crystal Random Cavities

“…Notably, the maximum Q factor was 3.4 × 10 5 in air and 2.0 × 10 5 in D2O. These values are in fact close to the ideal Q~10 6 imposed by scattering loss 59 in PhC cavities, indicating that Q factors of Anderson localized modes in silicon PhC waveguides are comparable to those that would be obtained in carefully engineered and fabricated defect cavities. Next, we measured the wavelength shifts of the localized modes by changing the NaCl concentrations in D2O, as shown in Fig.…”

“…Recent studies have shown the importance of optical sensors for the diagnoses of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the cause of COVID-19 1,2 . The photonic and plasmonic sensors have been used for the detection of coronavirus particles 3 , their viral genomes 4 , and the serological antibodies 5,6 .…”

Coronavirus and Carbon Nanotubes: Seeking Immunological Relationships to Discover Immunotherapeutic Possibilities

“…Studies have shown that colloidal nanoparticles conjugated with streptavidin can detect MERS-CoV. 144 This rapid detection capability, after 35 minutes, allows to visualize the result with the naked eye. Interestingly, the viral detection is around 10 copies/µL of MERS-CoV RNA.…”

The Application of Nanoparticles in Diagnosis and Treatment of Kidney Diseases

“…Recently, due to the coronavirus disease 2019 (COVID-19) pandemic, a lot of research has been carried out into using gold NPs functionalised with aptamer, antibodies or DNA/RNA oligonucleotides to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [ 48 , 49 , 50 ]. In addition, gold NPs functionalised with short antigenic epitopes are also useful in serodiagnosis because they detect the presence of SARS-CoV-2 IgG antibodies, which allow assessing the humoral response to infection or the effectiveness of vaccination [ 51 ].…”