Rational Zika vaccine design via the modulation of antigen membrane anchors in chimpanzee adenoviral vectors
Year: 2018
Type: article
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.
Source: Nature Communications
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
Institutions: University of Oxford, Jenner Institute, Beth Israel Deaconess Medical Center, Harvard University, Imperial College London, MRC University of Glasgow Centre for Virus Research, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Siriraj Hospital, Mahidol University, John Radcliffe Hospital
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,870
Awards: G2206474454, Arthropod-borne infections, Viral Hepatitis, Studies of immunopathogenesis in dengue virus infection., Protective efficacy and neutralisation to select an optimal Zika virus vaccine, G4594603996, The emergence of Zika virus in Brazil: investigating viral features and host responses to design preventive strategies., The dynamic of anti-dengue antibodies over time., G8540267532
OpenAlex ID: W2808947321