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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| Format: | Article |
| Language: | English |
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MDPI AG
2021-11-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/9/11/1287 |
| _version_ | 1827675257982418944 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:00:36Z |
| format | Article |
| id | doaj.art-d8938000f77d420cb0d46092de4bfad9 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T05:00:36Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-d8938000f77d420cb0d46092de4bfad92023-11-23T01:52:26ZengMDPI AGVaccines2076-393X2021-11-01911128710.3390/vaccines9111287A Novel Double Mosaic Virus-like Particle-Based Vaccine against SARS-CoV-2 Incorporates Both Receptor Binding Motif (RBM) and Fusion DomainXinyue Chang0Andris Zeltins1Mona O. Mohsen2Zahra Gharailoo3Lisha Zha4Xuelan Liu5Senta Walton6Monique Vogel7Martin F. Bachmann8Department of Rheumatology and Immunology, University Hospital Bern, 3010 Bern, SwitzerlandLatvian Biomedical Research & Study Center, Ratsupites 1, LV-1067 Riga, LatviaDepartment of Rheumatology and Immunology, University Hospital Bern, 3010 Bern, SwitzerlandDepartment of Rheumatology and Immunology, University Hospital Bern, 3010 Bern, SwitzerlandInternational Immunology Centre, Anhui Agricultural University, Hefei 230036, ChinaDepartment of Rheumatology and Immunology, University Hospital Bern, 3010 Bern, SwitzerlandSaiba GmbH, 8808 Pfäffikon, SwitzerlandDepartment of Rheumatology and Immunology, University Hospital Bern, 3010 Bern, SwitzerlandDepartment of Rheumatology and Immunology, University Hospital Bern, 3010 Bern, SwitzerlandCOVID-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.https://www.mdpi.com/2076-393X/9/11/1287COVID19SARS-CoV-2vaccinevirus-like particleCuMV<sub>TT</sub>-DF |
| spellingShingle | 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 Vaccines COVID19 SARS-CoV-2 vaccine virus-like particle CuMV<sub>TT</sub>-DF |
| title | 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_short | 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 |
| topic | COVID19 SARS-CoV-2 vaccine virus-like particle CuMV<sub>TT</sub>-DF |
| url | https://www.mdpi.com/2076-393X/9/11/1287 |
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