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Title: Rational Zika vaccine design via the modulation of antigen membrane anchors in chimpanzee adenoviral vectors
Authors: César López-Camacho
Peter Abbink
Rafael A. Larocca
Wanwisa Dejnirattisai
Michael Boyd
Alex Badamchi-Zadeh
Zoë R. Wallace
Jennifer Doig
Ricardo Sanchez Velazquez
Roberto Dias Lins Neto
Danilo F. Coelho
Young Chan Kim
Claire L. Donald
Ania Owsianka
Giuditta De Lorenzo
Alain Kohl
Sarah C. Gilbert
Lucy Dorrell
Juthathip Mongkolsapaya
Arvind H. Patel
Gavin R. Screaton
Dan H. Barouch
Adrian V.S. Hill
Arturo Reyes-Sandoval
University of Oxford
Fundacao Oswaldo Cruz
Imperial College London
Faculty of Medicine, Siriraj Hospital, Mahidol University
Nuffield Department of Clinical Medicine
Harvard Medical School
University of Glasgow
Keywords: Biochemistry, Genetics and Molecular Biology;Chemistry;Physics and Astronomy
Issue Date: 1-Dec-2018
Citation: Nature Communications. Vol.9, No.1 (2018)
Abstract: © 2018 The Author(s). 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 ΔTM 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.
ISSN: 20411723
Appears in Collections:Scopus 2018

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