Integrated Assessment of Humoral and Cellular SARS-CoV-2 Immunity Using ELISA and a Gold Nanoparticle-Based IGRA.
- 1Institute for the Application of Nuclear Energy INEP, University of Belgrade, Banatska 31b, 11080 Belgrade, Serbia.
- 2Faculty of Technology and Metallurgy, University of Belgrade, Karnegijeva 4, 11000 Belgrade, Serbia.
Abstract
Although SARS-CoV-2 immunity has been widely investigated, the relationship between antibody levels and cellular immune responses following different routes of exposure to SARS-CoV-2 remains not fully revealed. In this study, cellular immunity was assessed using a newly developed whole-blood interferon-gamma release assay (nano-IGRA) based on gold nanoparticle (AuNP)-conjugated SARS-CoV-2 antigens. AuNP-conjugated and soluble antigens were compared regarding interferon gamma (IFN-γ) responses and intra- and interassay reproducibility in 112 individuals with immunity acquired through infection, vaccination, or both. Humoral immunity was evaluated by enzyme-linked immunosorbent assay (ELISA). Overall, 88% of participants were seropositive. AuNP-conjugated Spike (S) and Nucleocapsid (N) SARS-CoV-2 antigens induced significantly higher IFN-γ responses than soluble antigens in all exposure groups (p < 0.001). AuNP conjugation reduced intraassay variability by 62.4% and 61.4% for S and N, respectively, and interassay variability by 71.7% and 68.3%, respectively. Antibody levels correlated significantly with IFN-γ responses to S (ρ = 0.358, p < 0.001) and N (ρ = 0.309, p < 0.001). An interesting finding is that cellular responses were also detected in some seronegative individuals. Nano-IGRA, based on a novel AuNP-based approach, provides antigen-specific cellular immune assessment, combining enhanced IFN-γ responses with improved reproducibility. Further studies should establish diagnostic cut-offs, sensitivity, specificity, and clinical performance.
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BibTeX
@article{todorovic2026integrated,
title = {{Integrated Assessment of Humoral and Cellular SARS-CoV-2 Immunity Using ELISA and a Gold Nanoparticle-Based IGRA.}},
author = {Aleksandra Todorović and Danica Ćujić and Zorica Knežević Jugović and Petar Uskoković and Dušica Stojanović and Marija Gnjatović},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198664},
url = {https://europepmc.org/article/MED/42883910},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrated Assessment of Humoral and Cellular SARS-CoV-2 Immunity Using ELISA and a Gold Nanoparticle-Based IGRA.
AU - Aleksandra Todorović
AU - Danica Ćujić
AU - Zorica Knežević Jugović
AU - Petar Uskoković
AU - Dušica Stojanović
AU - Marija Gnjatović
PY - 2026
DA - 2026/09/28
JO - International journal of molecular sciences
DO - 10.3390/ijms27198664
UR - https://europepmc.org/article/MED/42883910
AB - Although SARS-CoV-2 immunity has been widely investigated, the relationship between antibody levels and cellular immune responses following different routes of exposure to SARS-CoV-2 remains not fully revealed. In this study, cellular immunity was assessed using a newly developed whole-blood interferon-gamma release assay (nano-IGRA) based on gold nanoparticle (AuNP)-conjugated SARS-CoV-2 antigens. AuNP-conjugated and soluble antigens were compared regarding interferon gamma (IFN-γ) responses and intra- and interassay reproducibility in 112 individuals with immunity acquired through infection, vaccination, or both. Humoral immunity was evaluated by enzyme-linked immunosorbent assay (ELISA). Overall, 88% of participants were seropositive. AuNP-conjugated Spike (S) and Nucleocapsid (N) SARS-CoV-2 antigens induced significantly higher IFN-γ responses than soluble antigens in all exposure groups (p < 0.001). AuNP conjugation reduced intraassay variability by 62.4% and 61.4% for S and N, respectively, and interassay variability by 71.7% and 68.3%, respectively. Antibody levels correlated significantly with IFN-γ responses to S (ρ = 0.358, p < 0.001) and N (ρ = 0.309, p < 0.001). An interesting finding is that cellular responses were also detected in some seronegative individuals. Nano-IGRA, based on a novel AuNP-based approach, provides antigen-specific cellular immune assessment, combining enhanced IFN-γ responses with improved reproducibility. Further studies should establish diagnostic cut-offs, sensitivity, specificity, and clinical performance.
SN - 1422-0067
ER -