Zika virus-like particles bearing covalent dimer of envelope protein protect mice from lethal challenge

De Lorenzo, G. et al. (2021) Zika virus-like particles bearing covalent dimer of envelope protein protect mice from lethal challenge. Journal of Virology, 95(1), e01415-20. (doi: 10.1128/JVI.01415-20) (PMID:33028720) (PMCID:PMCID: PMC7737734)

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Abstract

Zika virus (ZIKV) envelope (E) protein is the major target of neutralizing antibodies in infected host, and thus represents a candidate of interest for vaccine design. However, a major concern in the development of vaccines against ZIKV and the related dengue virus is the induction of cross-reactive poorly neutralizing antibodies that can cause antibody-dependent enhancement (ADE) of infection. This risk necessitates particular care in vaccine design. Specifically, the engineered immunogens should have their cross-reactive epitopes masked, and they should be optimized for eliciting virus-specific strongly neutralizing antibodies upon vaccination. Here, we developed ZIKV subunit- and virus-like particle (VLP)-based vaccines displaying E in its wild type form, or E locked in a covalently linked dimeric (cvD) conformation to enhance the exposure of E dimers to the immune system. Compared with their wild-type derivatives, cvD immunogens elicited antibody with higher capacity of neutralizing virus infection of cultured cells. More importantly, these immunogens protected animals from lethal challenge with both the African and Asian lineages of ZIKV, impairing virus dissemination to brain and sexual organs. Moreover, the locked conformation of E reduced the exposure of epitopes recognized by cross-reactive antibodies and therefore showed a lower potential to induce ADE in vitro. Our data demonstrated a higher efficacy of the VLPs in comparison with the soluble dimer and support VLP-cvD as a promising ZIKV vaccine.

Item Type:Articles
Additional Information:This research is funded by the Department of Health and Social Care using UK Aid funding and is managed by the NIHR (AHP and AK); the UK Medical Research Council (MC_UU12014/2 and MC_UU_12014/8) (AHP and AK). The views expressed in this publication are those of the author(s) and not necessarily those of the Department of Health and Social Care. This project was also partially funded through the European Union’s Horizon 2020 research and innovation programme under ZikaPLAN grant agreement No 734584 (JME).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brewer, Professor James and Doig, Ms Jennifer and Sanchez Velazquez, Ricardo and Setthapramote, Dr Chayanee and Tandavanitj, Mr Rapeepat and De Lorenzo, Dr Giuditta and Edgar, Professor Julia and Patel, Professor Arvind and Scales, Dr Hannah and Kohl, Professor Alain
Creator Roles:
De Lorenzo, G.Conceptualization, Data curation, Formal analysis, Investigation, Project administration, Methodology, Supervision, Validation, Visualization, Writing – original draft, Writing – review and editing
Tandavanitj, R.Data curation, Formal analysis, Investigation, Validation, Visualization, Writing – original draft, Writing – review and editing
Doig, J.Data curation, Investigation, Writing – review and editing
Setthapramote, C.Investigation, Visualization, Writing – review and editing
Sanchez Velazquez, R.Investigation, Writing – review and editing
Scales, H.Resources, Writing – review and editing
Edgar, J.Resources, Writing – review and editing
Kohl, A.Funding acquisition, Resources, Writing – review and editing
Brewer, J.Resources, Writing – review and editing
Patel, A.Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing – original draft, Writing – review and editing
Authors: De Lorenzo, G., Tandavanitj, R., Doig, J., Setthapramote, C., Poggianella, M., Sanchez Velazquez, R., Scales, H., Edgar, J. M., Kohl, A., Brewer, J., Burrone, O. R., and Patel, A.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Virology
Publisher:American Society for Microbiology
ISSN:0022-538X
ISSN (Online):1098-5514
Published Online:07 October 2020
Copyright Holders:Copyright © 2020 De Lorenzo et al.
First Published:First published in Journal of Virology 95(1):e01415-20
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
Medical Research Council (MRC)MC_UU_12014/2
Medical Research Council (MRC)MC_UU_12014/8
173101ZikaPLANHugh WillisonEuropean Commission (EC)Willison, Professor HughIII - Immunology