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: | , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/d8938000f77d420cb0d46092de4bfad9 |
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| Sumario: | 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. |
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