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

Author

Listed:
  • Xiaojun Wei

    (University of South Carolina
    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
    University of Florida
    University of Florida)

  • John R. Monnier

    (University of South Carolina)

  • Hui Wang

    (University of South Carolina)

  • Tony Y. Hu

    (Tulane University School of Medicine
    Tulane University School of Medicine)

  • Chuanbing Tang

    (University of South Carolina)

  • Helmut Albrecht

    (University of South Carolina
    Prisma Health)

  • Chang Liu

    (University of South Carolina
    University of South Carolina)

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.

Suggested Citation

  • 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 & Chang Liu, 2022. "A click chemistry amplified nanopore assay for ultrasensitive quantification of HIV-1 p24 antigen in clinical samples," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34273-x
    DOI: 10.1038/s41467-022-34273-x
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    References listed on IDEAS

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    1. Gongpu Zhao & Juan R. Perilla & Ernest L. Yufenyuy & Xin Meng & Bo Chen & Jiying Ning & Jinwoo Ahn & Angela M. Gronenborn & Klaus Schulten & Christopher Aiken & Peijun Zhang, 2013. "Mature HIV-1 capsid structure by cryo-electron microscopy and all-atom molecular dynamics," Nature, Nature, vol. 497(7451), pages 643-646, May.
    2. Yuqin Wang & Xiaoyu Guan & Shanyu Zhang & Yao Liu & Sha Wang & Pingping Fan & Xiaoyu Du & Shuanghong Yan & Panke Zhang & Hong-Yuan Chen & Wenfei Li & Daoqiang Zhang & Shuo Huang, 2021. "Structural-profiling of low molecular weight RNAs by nanopore trapping/translocation using Mycobacterium smegmatis porin A," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Ke Sun & Changjian Zhao & Xiaojun Zeng & Yuejia Chen & Xin Jiang & Xianting Ding & Lu Gou & Haiyang Xie & Xinqiong Li & Xialin Zhang & Sheng Lin & Linqin Dou & Long Wei & Haofu Niu & Ming Zhang & Ruoc, 2019. "Active DNA unwinding and transport by a membrane-adapted helicase nanopore," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    4. Kevin J. Freedman & Lauren M. Otto & Aleksandar P. Ivanov & Avijit Barik & Sang-Hyun Oh & Joshua B. Edel, 2016. "Nanopore sensing at ultra-low concentrations using single-molecule dielectrophoretic trapping," Nature Communications, Nature, vol. 7(1), pages 1-9, April.
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