A protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection.
作者： Jose Luis Slon-Campos , Wanwisa Dejnirattisai , Brett W. Jagger , César López-Camacho , Wiyada Wongwiwat
DOI: 10.1038/S41590-019-0477-Z
关键词:
摘要: Infections with dengue virus (DENV) and Zika (ZIKV) can induce cross-reactive antibody responses. Two immunodominant epitopes-one to precursor membrane protein one the fusion loop epitope on envelope (E) protein-are recognized by antibodies1-3 that are not only poorly neutralizing, but also promote increased viral replication 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 DENV vaccines as induction neutralizing antibodies may prime an individual natural infection. In this report, we describe design production covalently stabilized E dimers, which lack do expose epitope. Immunization mice dimers induces dimer-specific antibodies, protect against challenge during pregnancy. Importantly, E-dimer-induced response does cross-react or
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