TY - JOUR
T1 - A protective Zika virus E-dimer-based subunit vaccine engineered to abrogate antibody-dependent enhancement of dengue infection
AU - Slon-Campos, Jose Luis
AU - Dejnirattisai, Wanwisa
AU - Jagger, Brett W.
AU - López-Camacho, César
AU - Wongwiwat, Wiyada
AU - Durnell, Lorellin A.
AU - Winkler, Emma S.
AU - Chen, Rita E.
AU - Reyes-Sandoval, Arturo
AU - Rey, Felix A.
AU - Diamond, Michael S.
AU - Mongkolsapaya, Juthathip
AU - Screaton, Gavin R.
N1 - Funding Information:
This work was supported by the Wellcome Trust (collaborative grant 203224/Z/16/Z to G.R.S. and J.M.), National Institute for Health Research Biomedical Research Centre Funding Scheme (to G.R.S.), Medical Research Council Newton fund (UK–Thailand joint initiative of infectious diseases grant MR/R020957/1 to J.M.), National Institutes of Health (grants R01 AI073755, R01 AI127828 and R01 HD091218 to M.S.D., and grant T32 AI007172 to B.W.J.), UK Department of Health and Social Care (projects 972216 and 971557 to A.R.-S.) and French Government’s Programme d’Investissements d’Avenir (Labex Integrative Biology of Emerging Infectious Diseases grant ANR-10-LABX-62-IBEID 4E AAP to F.A.R.). G.R.S. is supported as a Wellcome Trust Senior Investigator (grant 095541/A/11/Z). We thank Y. C. Kim and B. D. Jimenez for technical assistance.
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071686228&partnerID=8YFLogxK
U2 - 10.1038/s41590-019-0477-z
DO - 10.1038/s41590-019-0477-z
M3 - Letter
C2 - 31477918
AN - SCOPUS:85071686228
SN - 1529-2908
VL - 20
SP - 1291
EP - 1298
JO - Nature Immunology
JF - Nature Immunology
IS - 10
ER -