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 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 virus-like particles were used as VLP scaffold and both domains were genetically fused in the middle of CuMV subunits, which co-assembled into double mosaic particles (CuMV-DF). A single fusion mosaic particle (CuMV-FP) containing the fusion peptide only was used for comparison. The vaccines were produced in , and electron microscopy and dynamic light scattering confirmed their integrity and homogeneity. In addition, the CuMV-DF vaccine was well recognized by ACE2 receptor, indicating that the RBM was in native conformation. Both CuMV-FP and CuMV-DF vaccines induced high levels of high avidity IgG antibodies as well as IgA recognizing spike and RBD in the case of CuMV-DF. Both vaccine candidates induced virus-neutralizing antibodies indicating that the fusion peptide can independently induce virus-neutralizing antibodies. In contrast, CuMV-DF containing both RBM and fusion peptide induced a higher level of neutralizing antibodies suggesting that the new double mosaic vaccine candidate CuMV-DF consisting of two antigens in one VLP maybe an attractive candidate for scale-up in a bacterial fermentation process for clinical development.