Natural infection by Zika virus but not DNA vaccination consistently elicits antibodies that compete with two potently neutralising monoclonal antibodies targeting distinct epitopesResearch in context
Teresa C. Smith,
Daniel O. Espinoza,
Yerun Zhu,
Jaime A. Cardona-Ospina,
Natalie M. Bowman,
Sylvia Becker-Dreps,
Nadine Rouphael,
Alfonso J. Rodriguez-Morales,
Filemon Bucardo,
Srilatha Edupuganti,
Lakshmanane Premkumar,
Mark J. Mulligan,
Aravinda M. de Silva,
Matthew H. Collins
Affiliations
Teresa C. Smith
Rollins School of Public Health, Emory University, Atlanta, GA, USA
Daniel O. Espinoza
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
Yerun Zhu
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
Jaime A. Cardona-Ospina
Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de las Américas-Institución Universitaria Visión de las Américas, Pereira, Risaralda, Colombia; Emerging Infectious Diseases and Tropical Medicine Research Group, Instituto para la Investigación en Ciencias Biomédicas – Sci-Help, Pereira, Colombia
Natalie M. Bowman
Division of Infectious Diseases, Department of Medicine, University of North Carolina Chapel Hill School of Medicine, Chapel Hill, NC, USA
Sylvia Becker-Dreps
Department of Family Medicine, University of North Carolina Chapel Hill, Chapel Hill, NC, USA; Department of Epidemiology, University of North Carolina Chapel Hill, Chapel Hill, NC, USA
Nadine Rouphael
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
Alfonso J. Rodriguez-Morales
Grupo de Investigación Biomedicina, Faculty of Medicine, Fundación Universitaria Autónoma de las Américas-Institución Universitaria Visión de las Américas, Pereira, Risaralda, Colombia; Faculty of Health Sciences, Universidad Científica del Sur, Lima, Peru; Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Beirut, Lebanon
Filemon Bucardo
Department of Microbiology and Parasitology, Universidad Nacional Autónoma de Nicaragua-León, León, Nicaragua
Srilatha Edupuganti
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA
Lakshmanane Premkumar
Department of Microbiology and Immunology, University of North Carolina Chapel Hill, Chapel Hill, NC, USA
Mark J. Mulligan
NYU Langone Vaccine Center, New York, NY, USA
Aravinda M. de Silva
Department of Microbiology and Immunology, University of North Carolina Chapel Hill, Chapel Hill, NC, USA
Matthew H. Collins
Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA; Corresponding author.
Summary: 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), CDC BAA 2017-N-18041 (PI: A. M. de Silva), Thrasher Fund (PI: M. H. Collins), K22 AI137306 (PI: M. H. Collins).