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

Abstract

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

Virus-like particle vaccinology, from bench to bedside

“…Similar results were obtained with RBM fused to VLP AP205 [33]. In addition, we generated a double mosaic particle, which induced neutralizing antibodies against both RBM in S1 as well as the cleavage site in S2, a second, "minor" neutralizing epitope [34].…”

Heterologous expression of Chimeric hepatitis B core virus like particles harboring SARS-CoV2 epitope and evaluation of its immunization potential in mice

“…Moreover, as it was expected for the SARS-CoV-2 vaccine, in both with and without adjuvant conditions, the IgG titer was normally higher four weeks after injection than two weeks later. Similarly, mice immunization and IgG evaluation through a VLP-based developed vaccine for SARS-CoV-2 based on S1 and S2 epitopes showed that signi cant anti-spike IgG antibody was produced 28 days after the immunization program, during which two doses of vaccine were administered on days on 0 and 21 [47].…”

Chimeric Hepatitis B core virus-like particles harboring SARS-CoV2 epitope elicit a humoral immune response in mice

“…Moreover, as expected for the SARS-CoV-2 vaccine, in both with and without adjuvant conditions, the IgG titer was normally higher 4 weeks after injection than 2 weeks later. Similarly, mice immunization and IgG evaluation through a VLP-based developed vaccine for SARS-CoV-2 based on S1 and S2 epitopes showed that a significant amount of anti-spike IgG antibody was produced 28 days after the immunization program, during which two doses of vaccine were administered on days 0 and 21 [ 47 ]. Although the humoral immunity results indicate the immunoactivity of the recombinant protein vaccine and confirm its successful expression, introducing this antigenic protein as an efficient vaccine needs comprehensive cellular immunity evaluations.…”