Neutralization of Middle East Respiratory Syndrome coronavirus through a scalable nanoparticle vaccine

ABSTRACT

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 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 upscalable, we genetically fused the receptor-binding motif (RBM) of MERS-CoV Spike protein into cucumber- mosaic virus-like particles. 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 (mCuMVTT-MERS) consists of unmodified wild type monomers and genetically modified monomers displaying RBM, both co-assemble in a prokaryotic expression system. mCuMVTT-MERS vaccine is self-adjuvanted with ssRNA, a TLR7/8 ligand which is spontaneously packaged during the expression process in E. coli. The ability of the engineered vaccine to bind to MERS-CoV receptor DPP4 was tested in a competitive ELISA. To test the safety and immunogenicity of mCuMVTT-MERS Balb/cOlaHsd mice were primed with 100ug VLPs and boosted on day 28. The developed vaccine induced high anti-RBD and anti-Spike antibodies in a murine model, showing high binding avidity and the ability to completely neutralize MERS-CoV/EMC/2012 isolate, demonstrating the protective potential of the vaccine candidate in dromedaries and humans.