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

Author

Listed:
  • 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
    Mahidol University)

  • 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)

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.

Suggested Citation

  • 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 Net, 2018. "Rational Zika vaccine design via the modulation of antigen membrane anchors in chimpanzee adenoviral vectors," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04859-5
    DOI: 10.1038/s41467-018-04859-5
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