A protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection

Jose Luis Slon-Campos, Wanwisa Dejnirattisai, Brett W. Jagger, César López-Camacho, Wiyada Wongwiwat, Lorellin A. Durnell, Emma S. Winkler, Rita E. Chen, Arturo Reyes-Sandoval, Felix A. Rey, Michael S. Diamond, Juthathip Mongkolsapaya, Gavin R. Screaton

Research output: Contribution to journalLetter

13 Scopus citations

Abstract

Infections with dengue virus (DENV) and Zika virus (ZIKV) can induce cross-reactive antibody responses. Two immunodominant epitopes—one to precursor membrane protein and one to the fusion loop epitope on envelope (E) protein—are recognized by cross-reactive antibodies1–3 that are not only poorly neutralizing, but can also promote increased viral replication and disease severity via Fcγ receptor-mediated infection of myeloid cells—a process termed antibody-dependent enhancement (ADE)1,4,5. ADE is a significant concern for both ZIKV and DENV vaccines as the induction of poorly neutralizing cross-reactive antibodies may prime an individual for ADE on natural infection. In this report, we describe the design and production of covalently stabilized ZIKV E dimers, which lack precursor membrane protein and do not expose the immunodominant fusion loop epitope. Immunization of mice with ZIKV E dimers induces dimer-specific antibodies, which protect against ZIKV challenge during pregnancy. Importantly, the ZIKV E-dimer-induced response does not cross-react with DENV or induce ADE of DENV infection.

Original languageEnglish
Pages (from-to)1291-1298
Number of pages8
JournalNature immunology
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2019

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    Slon-Campos, J. L., Dejnirattisai, W., Jagger, B. W., López-Camacho, C., Wongwiwat, W., Durnell, L. A., Winkler, E. S., Chen, R. E., Reyes-Sandoval, A., Rey, F. A., Diamond, M. S., Mongkolsapaya, J., & Screaton, G. R. (2019). A protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection. Nature immunology, 20(10), 1291-1298. https://doi.org/10.1038/s41590-019-0477-z