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RATIONAL ZIKA VACCINE DESIGN VIA THE MODULATION OF ANTIGEN MEMBRANE ANCHORS IN CHIMPANZEE ADENOVIRAL VECTORS
López-Camacho, César et al. | Date Issued: 2018
Author
López-Camacho, César
Abbink, Peter
Larocca, Rafael A.
Dejnirattisai, Wanwisa
Boyd, Michael
Badamchi-Zadeh, Alex
Wallace, Zoë R.
Doig, Jennifer
Velazquez, Ricardo Sanchez
Neto, Roberto Dias Lins
Coelho, Danilo F.
Kim, Young Chan
Donald, Claire L.
Owsianka, Ania
De Lorenzo, Giuditta
Kohl, Alain
Gilbert, Sarah C.
Dorrell, Lucy
Mongkolsapaya, Juthathip
Patel, Arvind H.
Screaton, Gavin R.
Barouch, Dan H.
Hill, Adrian V. S.
Reyes-Sandoval, Arturo
Affilliation
Múltipla - ver em Notas
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.
Keywords in Portuguese
Vírus Zika
Vacina
Resposta imune
 
Keywords
Zika virus
Vaccine
Immune response
 
Citation
LÓPEZ-CAMACHO, C. et al. Rational Zika vaccine design via the modulation of antigen membrane anchors in chimpanzee adenoviral vectors. Nature Communications, v. 9, n. 1, p. 1-11, 22 Jun. 2018.
DOI
10.1038/s41467-018-04859-5
ISSN
2041-1723
Notes
1The Jenner Institute, Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Molecular Physiology, Roosevelt Drive, Oxford, OX3 7BN UK 2Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 USA 3Division of Immunology and Inflammation, Department of Medicine, Hammersmith Campus, Imperial College London, London, W12 0NN UK 4Nuffield Department of Medicine and Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, OX3 7FZ UK 5MRC-University of Glasgow Centre for Virus Research, University of Glasgow, Glasgow,, G61 1QH Scotland UK 6Aggeu Magalhães Institute, Oswaldo Cruz Foundation, 50670-465 Recife, Brazil 7The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ UK 8Dengue Hemorrhagic Fever Research Unit, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700 Thailand 9Division of Medical Sciences, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU UK