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: | Sanchez Velazquez, Ricardo and De Lorenzo, Dr Giuditta and Edgar, Professor Julia and Setthapramote, Dr Chayanee and Brewer, Professor James and Patel, Professor Arvind and Tandavanitj, Mr Rapeepat and Scales, Dr Hannah and Kohl, Professor Alain and Doig, Ms Jennifer |
| 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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| 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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