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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 publication




Journal article


Nature immunology

Publication Date





1291 - 1298


Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.


Animals, Mice, Inbred BALB C, Humans, Mice, Dengue Virus, Dengue, Receptors, IgG, Viral Envelope Proteins, Viral Vaccines, Antibodies, Viral, Epitopes, Immunodominant Epitopes, Vaccination, Genetic Engineering, Virus Replication, Cross Reactions, Dimerization, Female, Antibodies, Neutralizing, HEK293 Cells, Zika Virus, Zika Virus Infection