Design and characterization of chimeric Rabies-SARS-CoV-2 virus-like particles for vaccine purposes.

Content Provider	Europe PMC
Author	Garay, Ernesto Fontana, Diego Villarraza, Javier Fuselli, Antonela Gugliotta, Agustina Antuña, Sebastián Tardivo, Belén Rodríguez, María Celeste Gastaldi, Victoria Battagliotti, Juan Manuel Alvarez, Diego Castro, Eliana Cassataro, Juliana Ceaglio, Natalia Prieto, Claudio
Abstract	Due to the high number of doses required to achieve adequate coverage in the context of COVID-19 pandemics, there is a great need for novel vaccine developments. In this field, there have been research approaches that focused on the production of SARS-CoV-2 virus-like particles. These are promising vaccine candidates as their structure is similar to that of native virions but they lack the genome, constituting a biosafe alternative. In order to produce these structures using mammal cells, it has been established that all four structural proteins must be expressed. Here we report the generation and characterization of a novel chimeric virus-like particle (VLP) that can be produced by the expression of a single novel fusion protein that contains SARS-CoV-2 spike (S) ectodomain fused to rabies glycoprotein membrane anchoring region in HEK293 cells. This protein is structurally similar to native S and can autonomously bud forming enveloped VLPs that resemble native virions both in size and in morphology, displaying S ectodomain and receptor binding domain (RBD) on their surface. As a proof of concept, we analyzed the immunogenicity of this vaccine candidate in mice and confirmed the generation of anti-S, anti-RBD, and neutralizing antibodies.Key points• A novel fusion rabies glycoprotein containing S ectodomain was designed. • Fusion protein formed cVLPs that were morphologically similar to SARS-CoV-2 virions. • cVLPs induced anti-S, anti-RBD, and neutralizing antibodies in mice.
ISSN	01757598
Journal	Applied Microbiology and Biotechnology
Volume Number	107
PubMed Central reference number	PMC10150342
Issue Number	11
PubMed reference number	37126083
e-ISSN	14320614
DOI	10.1007/s00253-023-12545-w
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2023-05-01
Publisher Place	Berlin/Heidelberg
Access Restriction	Open
Rights License	This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
Subject Keyword	Spike Chimeric VLP RBD Rabies
Content Type	Text
Resource Type	Article
Subject	Medicine Applied Microbiology and Biotechnology Biotechnology