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Journal article

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

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-018-04859-5

Authors


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Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; CCMP
Role:
Author
ORCID:
0000-0001-7932-2341
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Role:
Author
ORCID:
0000-0003-1978-088X
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Role:
Author
ORCID:
0000-0002-9995-1804


Publisher:
Nature Publishing Group
Journal:
Nature Communications More from this journal
Volume:
9
Issue:
1
Publication date:
2018-06-22
Acceptance date:
2018-05-23
DOI:
EISSN:
2041-1723


Keywords:
Pubs id:
pubs:858959
UUID:
uuid:99b42002-53ab-40d8-9cc8-9737f02474b5
Local pid:
pubs:858959
Source identifiers:
858959
Deposit date:
2018-06-23

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