期刊
NPJ VACCINES
卷 6, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41541-021-00365-w
关键词
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资金
- MRC-HMC [29032016]
- Qatar National Research Fund [PDRA4-0118-18002]
- Swiss National Science Foundation [SNF 310030_185114, SNF 310030_179165]
- Swiss National Science Foundation (SNF) [310030_179165] Funding Source: Swiss National Science Foundation (SNF)
This study produced a nanovaccine based on VLPs against MERS-CoV, incorporating the RBM of the virus into the VLPs' surface to create a new immunologically optimized vaccine platform. The vaccine induced high antibody responses and demonstrated protective potential against MERS-CoV.
MERS-CoV continues to cause human outbreaks, so far in 27 countries worldwide following the first registered epidemic in Saudi Arabia in 2012. In this study, we produced a nanovaccine based on virus-like particles (VLPs). VLPs are safe vaccine platforms as they lack any replication-competent genetic material, and are used since many years against hepatitis B virus (HBV), hepatitis E virus (HEV) and human papilloma virus (HPV). In order to produce a vaccine that is readily scalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV spike protein into the surface of cucumber-mosaic virus VLPs. The employed CuMVTT-VLPs represent a new immunologically optimized vaccine platform incorporating a universal T cell epitope derived from tetanus toxin (TT). The resultant vaccine candidate (mCuMV(TT)-MERS) is a mosaic particle and consists of unmodified wild type monomers and genetically modified monomers displaying RBM, co-assembling within E. coli upon expression. mCuMV(TT)-MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the bacterial expression process. The developed vaccine candidate induced high anti-RBD and anti-spike antibodies in a murine model, showing high binding avidity and an ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate for dromedaries and humans.
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