A Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion Domain

COVID-19 has emerged, and has rapidly become a major health problem worldwide, causing millions of mortalities. Vaccination against COVID-19 is the most efficient way to stop the pandemic. The goal of vaccines is to induce neutralizing antibodies against SARS-CoV-2 virus. Here, we present a novel do...

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Autores principales:	Xinyue Chang, Andris Zeltins, Mona O. Mohsen, Zahra Gharailoo, Lisha Zha, Xuelan Liu, Senta Walton, Monique Vogel, Martin F. Bachmann
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	COVID19 SARS-CoV-2 vaccine virus-like particle CuMV<sub>TT</sub>-DF Medicine R
Acceso en línea:	https://doaj.org/article/d8938000f77d420cb0d46092de4bfad9
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spelling	oai:doaj.org-article:d8938000f77d420cb0d46092de4bfad92021-11-25T19:10:57ZA Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion Domain10.3390/vaccines91112872076-393Xhttps://doaj.org/article/d8938000f77d420cb0d46092de4bfad92021-11-01T00:00:00Zhttps://www.mdpi.com/2076-393X/9/11/1287https://doaj.org/toc/2076-393XCOVID-19 has emerged, and has rapidly become a major health problem worldwide, causing millions of mortalities. Vaccination against COVID-19 is the most efficient way to stop the pandemic. The goal of vaccines is to induce neutralizing antibodies against SARS-CoV-2 virus. Here, we present a novel double mosaic virus-like particle (VLP) displaying two independent neutralizing epitopes, namely the receptor binding motif (RBM) located in S1 and the fusion peptide (AA 817–855) located in S2. CuMV<sub>TT</sub> virus-like particles were used as VLP scaffold and both domains were genetically fused in the middle of CuMV<sub>TT</sub> subunits, which co-assembled into double mosaic particles (CuMV<sub>TT</sub>-DF). A single fusion mosaic particle (CuMV<sub>TT</sub>-FP) containing the fusion peptide only was used for comparison. The vaccines were produced in <i>E. coli</i>, and electron microscopy and dynamic light scattering confirmed their integrity and homogeneity. In addition, the CuMV<sub>TT</sub>-DF vaccine was well recognized by ACE2 receptor, indicating that the RBM was in native conformation. Both CuMV<sub>TT</sub>-FP and CuMV<sub>TT</sub>-DF vaccines induced high levels of high avidity IgG antibodies as well as IgA recognizing spike and RBD in the case of CuMV<sub>TT</sub>-DF. Both vaccine candidates induced virus-neutralizing antibodies indicating that the fusion peptide can independently induce virus-neutralizing antibodies. In contrast, CuMV<sub>TT</sub>-DF containing both RBM and fusion peptide induced a higher level of neutralizing antibodies suggesting that the new double mosaic vaccine candidate CuMV<sub>TT</sub>-DF consisting of two antigens in one VLP maybe an attractive candidate for scale-up in a bacterial fermentation process for clinical development.Xinyue ChangAndris ZeltinsMona O. MohsenZahra GharailooLisha ZhaXuelan LiuSenta WaltonMonique VogelMartin F. BachmannMDPI AGarticleCOVID19SARS-CoV-2vaccinevirus-like particleCuMV<sub>TT</sub>-DFMedicineRENVaccines, Vol 9, Iss 1287, p 1287 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID19 SARS-CoV-2 vaccine virus-like particle CuMV<sub>TT</sub>-DF Medicine R
spellingShingle	COVID19 SARS-CoV-2 vaccine virus-like particle CuMV<sub>TT</sub>-DF Medicine R Xinyue Chang Andris Zeltins Mona O. Mohsen Zahra Gharailoo Lisha Zha Xuelan Liu Senta Walton Monique Vogel Martin F. Bachmann A Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion Domain
description	COVID-19 has emerged, and has rapidly become a major health problem worldwide, causing millions of mortalities. Vaccination against COVID-19 is the most efficient way to stop the pandemic. The goal of vaccines is to induce neutralizing antibodies against SARS-CoV-2 virus. Here, we present a novel double mosaic virus-like particle (VLP) displaying two independent neutralizing epitopes, namely the receptor binding motif (RBM) located in S1 and the fusion peptide (AA 817–855) located in S2. CuMV<sub>TT</sub> virus-like particles were used as VLP scaffold and both domains were genetically fused in the middle of CuMV<sub>TT</sub> subunits, which co-assembled into double mosaic particles (CuMV<sub>TT</sub>-DF). A single fusion mosaic particle (CuMV<sub>TT</sub>-FP) containing the fusion peptide only was used for comparison. The vaccines were produced in <i>E. coli</i>, and electron microscopy and dynamic light scattering confirmed their integrity and homogeneity. In addition, the CuMV<sub>TT</sub>-DF vaccine was well recognized by ACE2 receptor, indicating that the RBM was in native conformation. Both CuMV<sub>TT</sub>-FP and CuMV<sub>TT</sub>-DF vaccines induced high levels of high avidity IgG antibodies as well as IgA recognizing spike and RBD in the case of CuMV<sub>TT</sub>-DF. Both vaccine candidates induced virus-neutralizing antibodies indicating that the fusion peptide can independently induce virus-neutralizing antibodies. In contrast, CuMV<sub>TT</sub>-DF containing both RBM and fusion peptide induced a higher level of neutralizing antibodies suggesting that the new double mosaic vaccine candidate CuMV<sub>TT</sub>-DF consisting of two antigens in one VLP maybe an attractive candidate for scale-up in a bacterial fermentation process for clinical development.
format	article
author	Xinyue Chang Andris Zeltins Mona O. Mohsen Zahra Gharailoo Lisha Zha Xuelan Liu Senta Walton Monique Vogel Martin F. Bachmann
author_facet	Xinyue Chang Andris Zeltins Mona O. Mohsen Zahra Gharailoo Lisha Zha Xuelan Liu Senta Walton Monique Vogel Martin F. Bachmann
author_sort	Xinyue Chang
title	A Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion Domain
title_short	A Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion Domain
title_full	A Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion Domain
title_fullStr	A Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion Domain
title_full_unstemmed	A Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion Domain
title_sort	novel double mosaic virus-like particle-based vaccine against sars-cov-2 incorporates both receptor binding motif (rbm) and fusion domain
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d8938000f77d420cb0d46092de4bfad9
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A Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion Domain

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