A click chemistry amplified nanopore assay for ultrasensitive quantification of HIV-1 p24 antigen in clinical samples

Xiaojun Wei, Xiaoqin Wang, Zehui Zhang, Yuanyuan Luo, Zixin Wang, Wen Xiong, Piyush K. Jain, John R. Monnier, Hui Wang, Tony Y. Hu, Chuanbing Tang, Helmut Albrecht and Chang Liu ()
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Xiaojun Wei: University of South Carolina
Xiaoqin Wang: University of South Carolina
Zehui Zhang: University of South Carolina
Yuanyuan Luo: University of South Carolina
Zixin Wang: University of South Carolina
Wen Xiong: University of South Carolina
Piyush K. Jain: University of Florida
John R. Monnier: University of South Carolina
Hui Wang: University of South Carolina
Tony Y. Hu: Tulane University School of Medicine
Chuanbing Tang: University of South Carolina
Helmut Albrecht: University of South Carolina
Chang Liu: University of South Carolina

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Despite major advances in HIV testing, ultrasensitive detection of early infection remains challenging, especially for the viral capsid protein p24, which is an early virological biomarker of HIV-1 infection. Here, To improve p24 detection in patients missed by immunological tests that dominate the diagnostics market, we show a click chemistry amplified nanopore (CAN) assay for ultrasensitive quantitative detection. This strategy achieves a 20.8 fM (0.5 pg/ml) limit of detection for HIV-1 p24 antigen in human serum, demonstrating 20~100-fold higher analytical sensitivity than nanocluster-based immunoassays and clinically used enzyme-linked immunosorbent assay, respectively. Clinical validation of the CAN assay in a pilot cohort shows p24 quantification at ultra-low concentration range and correlation with CD4 count and viral load. We believe that this strategy can improve the utility of p24 antigen in detecting early infection and monitoring HIV progression and treatment efficacy, and also can be readily modified to detect other infectious diseases.

Date: 2022
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DOI: 10.1038/s41467-022-34273-x

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