Natural infection by Zika virus but not DNA vaccination consistently elicits antibodies that compete with two potently neutralising monoclonal antibodies targeting distinct epitopes

• Type of Material: Article
• Authors: Teresa C. Smith, Emory University; Daniel Omar Espinoza, Emory University; Yerun Zhu, Emory University; Jaime A. Cardona-Ospina, Universitaria Visión de las Américas; Natalie M. Bowman, University of North Carolina, Chapel Hill; Sylvia Becker-Dreps, University of North Carolina, Chapel Hill; Nadine Rouphael, Emory University; Alfonso J. Rodriguez-Morales, Universitaria Visión de las Américas; Filemon Bucardo, Universidad Nacional Autónoma de Nicaragua-León; Sri Edupuganti, Emory University; Lakshmanane Premkumar, University of North Carolina, Chapel Hill; Mark J. Mulligan, New York University; Aravinda M. de Silva, University of North Carolina, Chapel Hill; Matthew Collins, Emory University
• Language: English
• Date: 2023-11-18
• Publisher: Elsevier
• Publication Version: Final Published Version
• Copyright Statement: © 2023 The Author(s). Published by Elsevier B.V.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1016/j.ebiom.2023.104875
• Title of Journal or Parent Work: EBioMedicine
• Volume: 98
• Start Page: 104875
• Grant/Funding Information: 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).
• Keywords: Virus neutralisation; Humoral immunity; Type-specific antibody; Zika; Vaccinology
• Research Categories: Health Sciences, Immunology; Health Sciences, Public Health; Biology, Virology; Health Sciences, Epidemiology

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.