Diagnosis of Zika virus infection on a nanotechnology platform

Journal name:
Nature Medicine
Volume:
23,
Pages:
548–550
Year published:
DOI:
doi:10.1038/nm.4302
Received
Accepted
Published online

We developed a multiplexed assay on a plasmonic-gold platform for measuring IgG and IgA antibodies and IgG avidity against both Zika virus (ZIKV) and dengue virus (DENV) infections. In contrast to IgM cross-reactivity, IgG and IgA antibodies against ZIKV nonstructural protein 1 (NS1) antigen were specific to ZIKV infection, and IgG avidity revealed recent ZIKV infection and past DENV-2 infection in patients in dengue-endemic regions. This assay could enable specific diagnosis of ZIKV infection over other flaviviral infections.

At a glance

Figures

  1. ZIKV and DENV IgG, IgM, IgA and IgG avidity levels, as measured using the pGOLD platform, for three groups of individuals: a cohort of 29 patients with ZIKV infection (Group1_Z), a cohort of 64 patients with DENV infection (Group2_D) and a control group of 50 samples (Group3_H).
    Figure 1: ZIKV and DENV IgG, IgM, IgA and IgG avidity levels, as measured using the pGOLD platform, for three groups of individuals: a cohort of 29 patients with ZIKV infection (Group1_Z), a cohort of 64 patients with DENV infection (Group2_D) and a control group of 50 samples (Group3_H).

    (ac) Box plots for ZIKV IgG, IgM and IgA antibody levels, respectively, for the three groups; signals are relative. (df) Comparison of ZIKV IgG, IgM and IgA levels in Group1_Z patients with ZIKV infection according to days between onset of illness and sample collection. Patients with ZIKV infection are differentiated into four subgroups on the basis of the number of days between onset of illness and sample collection: 1–7 d; 8–15 d; 16–50 d; and 51–100 d. (g) Box plot showing DENV IgG antibody levels for the three groups. (h) Box plot of DENV IgG avidity levels for serum specimens from Group2_D and Group1_Z. (i) Box plot showing ZIKV IgG avidity levels according to days between onset of illness and sample collection. All tests were performed three times, with an average of three measurements presented here. Error bars presented in df demonstrate the s.d. of three measurements for each sample. For box plots, measurement data (points) with median value (center line), average value (center small box), 1%, 25%, 75% and 99% value lines (box lines) are presented.

  2. Serology of acute ZIKV infection in patients positive for ZIKV RNA in serum (Group4_Z) and acute secondary DENV infection in patients positive for DENV RNA in serum (Group5_DD).
    Figure 2: Serology of acute ZIKV infection in patients positive for ZIKV RNA in serum (Group4_Z) and acute secondary DENV infection in patients positive for DENV RNA in serum (Group5_DD).

    (a) Box plot showing ZIKV IgG antibody levels for serum specimens from three groups of patients: eight patients with secondary DENV infection and detectable DENV RNA (Group5_DD); 49 patients with secondary ZIKV infection and detectable ZIKV RNA (Group4_Z); and 50 patients with no known history of ZIKV or DENV infection (Group3_H). (b) ZIKV IgG avidity levels for Group4_Z and Group1_Z patients. (c) Box plot for DENV IgG antibody levels for serum specimens from the three groups of patients as described in a. (d) Box plot of DENV IgG avidity levels for serum specimens from Group5_DD and Group4_Z patients. (e,f) Box plot showing ZIKV IgA and DENV IgA antibody levels for serum specimens from the three groups of patients as described in a. All tests were performed three times; the average of three measurements is presented. For box plots, measurement data (points) with median value (center line), average value (center small box), 1%, 25%, 75% and 99% value lines (box lines) are presented.

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Author information

  1. These authors contributed equally to this work.

    • Bo Zhang &
    • Benjamin A Pinsky

Affiliations

  1. Nirmidas Biotech, Palo Alto, California, USA.

    • Bo Zhang,
    • Jeyarama S Ananta,
    • Su Zhao,
    • Shylaja Arulkumar,
    • Clay Hopes &
    • Meijie Tang
  2. Department of Pathology, Stanford University School of Medicine, Stanford, California, USA.

    • Benjamin A Pinsky &
    • Malaya K Sahoo
  3. Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California, USA.

    • Benjamin A Pinsky
  4. Department of Materials Science and Engineering, South University of Science and Technology of China, Shenzhen, China.

    • Hao Wan
  5. Medical Research Institute, Colombo, Sri Lanka.

    • Janaki Abeynayake
  6. Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia, USA.

    • Jesse J Waggoner
  7. Department of Chemistry, Stanford University, Stanford, California, USA.

    • Hongjie Dai

Contributions

B.Z., M.T. and H.D. conceived of the study. B.Z., B.A.P. and H.D. designed the experiments. J.A. and B.A.P. provided serum samples. B.Z., J.S.A., S.A., S.Z., H.W., M.K.S. and C.H. conducted the experiments. B.Z., J.J.W., B.A.P. and H.D. analyzed the data and wrote the manuscript.

Competing financial interests

H. Dai is a scientific adviser and share-holder of Nirmidas Biotech and served as a consultant for this work. The pGOLD platform was licensed to Nirmidas Biotech by Stanford University.

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