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

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 Lorenzo, Alain Kohl, Sarah C. Gilbert, Lucy Dorrell, Juthathip Mongkolsapaya, Arvind H. Patel, Gavin R. Screaton, Dan H. Barouch, Adrian V. S. Hill and Arturo Reyes-Sandoval ()
Additional contact information
César López-Camacho: The Henry Wellcome Building for Molecular Physiology
Peter Abbink: Harvard Medical School
Rafael A. Larocca: Harvard Medical School
Wanwisa Dejnirattisai: Imperial College London
Michael Boyd: Harvard Medical School
Alex Badamchi-Zadeh: Harvard Medical School
Zoë R. Wallace: University of Oxford
Jennifer Doig: University of Glasgow
Ricardo Sanchez Velazquez: University of Glasgow
Roberto Dias Lins Neto: Oswaldo Cruz Foundation
Danilo F. Coelho: Oswaldo Cruz Foundation
Young Chan Kim: The Henry Wellcome Building for Molecular Physiology
Claire L. Donald: University of Glasgow
Ania Owsianka: University of Glasgow
Giuditta Lorenzo: University of Glasgow
Alain Kohl: University of Glasgow
Sarah C. Gilbert: University of Oxford
Lucy Dorrell: University of Oxford
Juthathip Mongkolsapaya: Imperial College London
Arvind H. Patel: University of Glasgow
Gavin R. Screaton: University of Oxford
Dan H. Barouch: Harvard Medical School
Adrian V. S. Hill: University of Oxford
Arturo Reyes-Sandoval: The Henry Wellcome Building for Molecular Physiology

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04859-5

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