[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]
Nat Immunol. 2019 Sep 2. doi: 10.1038/s41590-019-0477-z. [Epub ahead of print]
A protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection.
Slon-Campos JL1, Dejnirattisai W1, Jagger BW2,3, López-Camacho C4, Wongwiwat W1, Durnell LA2, Winkler ES2, Chen RE2, Reyes-Sandoval A4, Rey FA5,6, Diamond MS2,7,8,9, Mongkolsapaya J10,11, Screaton GR12.
Author information: 1 Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. 2 Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA. 3 Department of Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo, MI, USA. 4 Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK. 5 Unité de Virologie Structurale, Département de Virologie, Institut Pasteur, Paris, France. 6 Centre National de la Recherche Scientifique, Unité Mixte de Recherche 3569, Paris, France. 7 Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO, USA. 8 Department of Molecular Microbiology, Washington University School of Medicine, Saint Louis, MO, USA. 9 Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, Saint Louis, MO, USA. 10 Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. firstname.lastname@example.org. 11 Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. email@example.com. 12 Division of Medical Sciences, University of Oxford, Oxford, UK. firstname.lastname@example.org.
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 antibodies1-3that 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.
PMID: 31477918 DOI: 10.1038/s41590-019-0477-z
Keywords: Zika Virus; Vaccines; A.D.E.; Dengue fever; Animal models.