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SARS-CoV-2 Virus like Particles produced by a single recombinant baculovirus generate potent neutralizing antibody that protects against variant challenge

Edward Sullivan, Po-Yu Sung, Weining Wu, Neil Berry, Sarah Kempster, Deborah Ferguson, Neil Almond, Ian M. Jones, Polly Roy
doi: https://doi.org/10.1101/2021.11.29.470349
Edward Sullivan
1Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
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Po-Yu Sung
1Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
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Weining Wu
1Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
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Neil Berry
2Division of Infectious Disease Diagnostics, National Institute for Biological Standards and Control, Potters Bar EN6 3QG, UK
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Sarah Kempster
2Division of Infectious Disease Diagnostics, National Institute for Biological Standards and Control, Potters Bar EN6 3QG, UK
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Deborah Ferguson
2Division of Infectious Disease Diagnostics, National Institute for Biological Standards and Control, Potters Bar EN6 3QG, UK
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Neil Almond
2Division of Infectious Disease Diagnostics, National Institute for Biological Standards and Control, Potters Bar EN6 3QG, UK
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Ian M. Jones
3School of Biological Sciences, University of Reading, Reading RG6 6AH, UK
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Polly Roy
1Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
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  • For correspondence: Polly.Roy@lshtm.ac.uk
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ABSTRACT

The Covid-19 pandemic caused by SARS-CoV-2 infection has highlighted the need for the rapid generation of efficient vaccines for emerging disease. Virus-like particles, VLPs, are an established vaccine technology that produces virus-like mimics, based on expression of the structural proteins of a target virus that can stimulate strong neutralizing antibody responses. SARS-CoV-2 is a coronavirus where the basis of VLP formation has been shown to be the co-expression of the spike, membrane and envelope structural proteins. Here we describe the generation of SARS-CoV-2 VLPs by the co-expression of the salient structural proteins in insect cells using the established baculovirus expression system. VLPs were heterologous ∼100nm diameter enveloped particles with a distinct fringe that reacted strongly with SARS-CoV-2 convalescent sera. In a Syrian hamster challenge model, a non-adjuvanted VLPs induced neutralizing antibodies to the VLP-associated Wuhan S protein, reduced virus shedding following a virulent challenge with SARS-CoV-2 (B.1.1.7 variant) and protected against disease associated weight loss. Immunized animals showed reduced lung pathology and lower challenge virus replication than the non-immunized controls. Our data, using an established and scalable technology, suggest SARS-CoV-2 VLPs offer an efficient vaccine that mitigates against virus load and prevents severe disease.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted November 30, 2021.
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SARS-CoV-2 Virus like Particles produced by a single recombinant baculovirus generate potent neutralizing antibody that protects against variant challenge
Edward Sullivan, Po-Yu Sung, Weining Wu, Neil Berry, Sarah Kempster, Deborah Ferguson, Neil Almond, Ian M. Jones, Polly Roy
bioRxiv 2021.11.29.470349; doi: https://doi.org/10.1101/2021.11.29.470349
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SARS-CoV-2 Virus like Particles produced by a single recombinant baculovirus generate potent neutralizing antibody that protects against variant challenge
Edward Sullivan, Po-Yu Sung, Weining Wu, Neil Berry, Sarah Kempster, Deborah Ferguson, Neil Almond, Ian M. Jones, Polly Roy
bioRxiv 2021.11.29.470349; doi: https://doi.org/10.1101/2021.11.29.470349

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