AI Article Synopsis

  • The Zika virus has caused autochthonous transmission in 87 countries since 2015, posing risks like Guillain-Barré syndrome and complications in pregnancy, underscoring an urgent need for effective vaccines and enhanced understanding of immunity against ZIKV.
  • Researchers developed a new diagnostic test called blockade-of-binding (BOB) ELISA, using specific monoclonal antibodies to differentiate ZIKV from other flaviviruses, and found it performed better than traditional tests in validating ZIKV infections and assessing vaccine responses.
  • The BOB assays demonstrated high sensitivity and specificity in detecting antibodies from recent and past ZIKV infections, indicating potential for broader applications in monitoring ZIKV immunity and evaluating vaccine efficacy.

Article Abstract

Background: Autochthonous transmission of Zika virus (ZIKV) has been reported in 87 countries since 2015. Although most infections are mild, there is risk of Guillain-Barré syndrome and adverse pregnancy outcomes. Vaccines are urgently needed to prevent Zika, but sufficient understanding of humoral responses and tools to assess ZIKV-specific immunity are lacking.

Methods: We developed a blockade-of-binding (BOB) ELISA using A9E and G9E, two strongly neutralising ZIKV-specific monoclonal antibodies, which do not react with dengue virus. Receiver operating characteristic curve analysis assessed A9E and G9E BOB serodiagnostic performance. BOB was then applied to samples from a surveillance cohort in Risaralda, Colombia, and phase 1 ZIKV vaccine trial samples, comparing results against traditional serologic tests.

Findings: In the validation sample set (n = 120), A9E BOB has a sensitivity of 93.5% (95% CI: 79.3, 98.9) and specificity 97.8 (95% CI: 92.2, 99.6). G9E BOB had a sensitivity of 100% (95% CI: 89.0, 100.0) and specificity 100% (95% CI: 95.9, 100). Serum from natural infections consistently tested positive in these assays for up to one year, and reactivity tracks well with ZIKV infection status among sera from endemic areas with complicated flavivirus exposures. Interestingly, a leading ZIKV vaccine candidate elicited minimal BOB reactivity despite generating neutralising antibody responses.

Interpretation: In conclusion, A9E and G9E BOB assays are sensitive and specific assays for detecting antibodies elicited by recent or remote ZIKV infections. Given the additional ability of these BOB assays to detect immune responses that target different epitopes, further development of these assays is well justified for applications including flavivirus surveillance, translational vaccinology research and as potential serologic correlates of protective immunity against Zika.

Funding: R21 AI129532 (PI: S. Becker-Dreps), CDCBAA 2017-N-18041 (PI: A. M. de Silva), Thrasher Fund (PI: M. H. Collins), K22 AI137306 (PI: M. H. Collins).

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694573PMC
http://dx.doi.org/10.1016/j.ebiom.2023.104875DOI Listing

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