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

López-Camacho, C. et al. (2018) Rational Zika vaccine design via the modulation of antigen membrane anchors in chimpanzee adenoviral vectors. Nature Communications, 9, 2441. (doi: 10.1038/s41467-018-04859-5) (PMID:29934593) (PMCID:PMC6015009)

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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.

Item Type:Articles
Additional Information:A.R.-S., A.V.S.H. and S.C.G. are Jenner Investigators and an Oxford Martin Fellows. R.D.L.N. and D.F.C. were supported by Capes, Facepe, CNPq and LNCC. This report is independent research funded by the UK Department of Health and Social Care through Innovate UK “New vaccines for global epidemics: development and manufacture” grant No. 972216 (A.R.-S.), and also funded from an ODA budget (Global Health (ODA), 16/107/05—Design, development and GMP manufacture of a Zika vaccine) (A.H.P. and A.R-S). Juthathip Mongkolsapaya is supported by an MRC-Newton Fund grant, Gavin Screaton is a Wellcome Trust Senior Investigator.
Glasgow Author(s) Enlighten ID:De Lorenzo, Dr Giuditta and Owsianka, Dr Anna and Doig, Ms Jennifer and Sanchez Velazquez, Ricardo and Patel, Professor Arvind and Donald, Dr Claire and Kohl, Professor Alain
Authors: López-Camacho, C., Abbink, P., Larocca, R. A., Dejnirattisai, W., Boyd, M., Badamchi-Zadeh, A., Wallace, Z. R., Doig, J., Sanchez Velazquez, R., Neto, R. D. L., Coelho, D. F., Kim, Y. C., Donald, C. L., Owsianka, A., De Lorenzo, G., Kohl, A., Gilbert, S. C., Dorrell, L., Mongkolsapaya, J., Patel, A. H., Screaton, G. R., Barouch, D. H., Hill, A. V.S., and Reyes-Sandoval, A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Nature Communications
Publisher:Nature Research
ISSN (Online):2041-1723
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Nature Communications 9:2441
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656341Virus-host interactions in hepatitis C virus infectionJohn McLauchlanMedical Research Council (MRC)MC_UU_12014/1MVLS III - CENTRE FOR VIRUS RESEARCH
708681The emergence of Zika virus in Brazil: investigating prevalence and host responses to design preventive strategiesAlain KohlMedical Research Council (MRC)MR/N017552/1MVLS III - CENTRE FOR VIRUS RESEARCH