TY - JOUR
T1 - Nanoparticle-supported, rapid, digital quantification of neutralizing antibodies against SARS-CoV-2 variants
AU - Mirjalili, Seyedsina
AU - Ikbal, Md Ashif
AU - Hou, Ching Wen
AU - Mohammadi, Maziyar Kalateh
AU - Choi, Yeji
AU - Kelbauskas, Laimonas
AU - VanBlargan, Laura A.
AU - Hogue, Brenda G.
AU - Murugan, Vel
AU - Diamond, Michael S.
AU - Wang, Chao
N1 - Publisher Copyright:
© 2025 Elsevier B.V.
PY - 2025/10/1
Y1 - 2025/10/1
N2 - The measurement of neutralizing immune responses to viral infection is essential, given the heterogeneity of human immunity and the emergence of new virus strains. However, neutralizing antibody (nAb) assays often require high-level biosafety containment, sophisticated instrumentation, and long detection times. Here, as a proof-of-principle, we designed a nanoparticle-supported, rapid, electronic detection (NasRED) assay to assess the neutralizing potency of monoclonal antibodies (mAbs) against SARS-CoV-2. The gold nanoparticles (AuNPs) coated with human angiotensin-converting enzyme 2 (ACE2) protein as nAb potency reporters were mixed with the mAbs to be tested, as well as streptavidin-conjugated multivalent spike (S) protein or their receptor binding domains (RBD). High-affinity and ACE2-competitive nAbs alter the S (or RBD)-to-ACE2 binding level and modulate AuNP cluster formation and precipitation. The amount of free-floating AuNP reporters is quantified by a semiconductor-based readout system that measures the AuNPs' optical extinction, producing nAb signals that can differentiate SARS-CoV-2 variants (Wuhan-Hu-1, Gamma, and Omicron). The modular design nature, short assay time (less than 30 min), and portable and inexpensive readout system make this NasRED-nAb assay applicable to measuring vaccine potency, immune responses to infection, and the efficacy of antibody-based therapies.
AB - The measurement of neutralizing immune responses to viral infection is essential, given the heterogeneity of human immunity and the emergence of new virus strains. However, neutralizing antibody (nAb) assays often require high-level biosafety containment, sophisticated instrumentation, and long detection times. Here, as a proof-of-principle, we designed a nanoparticle-supported, rapid, electronic detection (NasRED) assay to assess the neutralizing potency of monoclonal antibodies (mAbs) against SARS-CoV-2. The gold nanoparticles (AuNPs) coated with human angiotensin-converting enzyme 2 (ACE2) protein as nAb potency reporters were mixed with the mAbs to be tested, as well as streptavidin-conjugated multivalent spike (S) protein or their receptor binding domains (RBD). High-affinity and ACE2-competitive nAbs alter the S (or RBD)-to-ACE2 binding level and modulate AuNP cluster formation and precipitation. The amount of free-floating AuNP reporters is quantified by a semiconductor-based readout system that measures the AuNPs' optical extinction, producing nAb signals that can differentiate SARS-CoV-2 variants (Wuhan-Hu-1, Gamma, and Omicron). The modular design nature, short assay time (less than 30 min), and portable and inexpensive readout system make this NasRED-nAb assay applicable to measuring vaccine potency, immune responses to infection, and the efficacy of antibody-based therapies.
KW - COVID-19
KW - Metal nanoparticles
KW - Neutralizing assay
KW - Rapid electronic detection
KW - SARS-CoV-2 variants
UR - https://www.scopus.com/pages/publications/105005207197
U2 - 10.1016/j.bios.2025.117549
DO - 10.1016/j.bios.2025.117549
M3 - Article
C2 - 40383030
AN - SCOPUS:105005207197
SN - 0956-5663
VL - 285
JO - Biosensors and Bioelectronics
JF - Biosensors and Bioelectronics
M1 - 117549
ER -