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Nat Commun. 2018 Jun 22;9(1):2441. doi: 10.1038/s41467-018-04859-5.

Rational Zika vaccine design via the modulation of antigen membrane anchors in chimpanzee adenoviral vectors.

Author information

1
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford, OX3 7BN, UK.
2
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.
3
Division of Immunology and Inflammation, Department of Medicine, Hammersmith Campus, Imperial College London, London, W12 0NN, UK.
4
Nuffield Department of Medicine and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, OX3 7FZ, UK.
5
MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow,, G61 1QH, Scotland, UK.
6
Aggeu Magalhães Institute, Oswaldo Cruz Foundation, 50670-465, Recife, Brazil.
7
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK.
8
Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand.
9
Division of Medical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU, UK.
10
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford, OX3 7BN, UK. arturo.reyes@ndm.ox.ac.uk.

Abstract

Zika virus (ZIKV) emerged on a global scale and no licensed vaccine ensures long-lasting anti-ZIKV immunity. Here we report the design and comparative evaluation of four replication-deficient chimpanzee adenoviral (ChAdOx1) ZIKV vaccine candidates comprising the addition or deletion of precursor membrane (prM) and envelope, with or without its transmembrane domain (TM). A single, non-adjuvanted vaccination of ChAdOx1 ZIKV vaccines elicits suitable levels of protective responses in mice challenged with ZIKV. ChAdOx1 prME ∆TM encoding prM and envelope without TM provides 100% protection, as well as long-lasting anti-envelope immune responses and no evidence of in vitro antibody-dependent enhancement to dengue virus. Deletion of prM and addition of TM reduces protective efficacy and yields lower anti-envelope responses. Our finding that immunity against ZIKV can be enhanced by modulating antigen membrane anchoring highlights important parameters in the design of viral vectored ZIKV vaccines to support further clinical assessments.

PMID:
29934593
PMCID:
PMC6015009
DOI:
10.1038/s41467-018-04859-5
[Indexed for MEDLINE]
Free PMC Article

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