Neutralization of MERS coronavirus through a scalable nanoparticle vaccine

Area of Science:

• Virology
• Vaccinology
• Nanotechnology

Background:

• Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks pose a global health threat, first identified in Saudi Arabia in 2012.
• Virus-like particles (VLPs) are established, safe vaccine platforms lacking genetic material, utilized for Hepatitis B, E, and Human Papillomavirus.
• Developing scalable and effective vaccines against emerging infectious diseases like MERS-CoV is crucial.

Purpose of the Study:

• To develop a scalable nanovaccine candidate against MERS-CoV using a novel virus-like particle (VLP) platform.
• To genetically engineer VLPs to display the MERS-CoV spike protein's receptor-binding motif (RBM).
• To evaluate the immunogenicity and neutralizing capacity of the developed nanovaccine in a preclinical model.

Main Methods:

• Genetically fused the MERS-CoV RBM onto cucumber mosaic virus VLPs (CuMV_TT-VLPs), incorporating a tetanus toxin T cell epitope.
• Co-expressed modified and unmodified monomers in E. coli to form mosaic VLPs (mCuMV_TT-MERS).
• Assessed antibody production (anti-RBD, anti-spike), binding avidity, and MERS-CoV neutralization in a murine model.

Main Results:

• The mCuMV_TT-MERS vaccine candidate self-adjuvanted with ssRNA (a TLR7/8 ligand) was successfully produced.
• Induced high levels of anti-RBD and anti-spike antibodies with significant binding avidity in mice.
• Demonstrated complete neutralization of the MERS-CoV/EMC/2012 isolate, indicating protective efficacy.

Conclusions:

• The developed mCuMV_TT-MERS nanovaccine is a promising candidate for preventing MERS-CoV infections.
• The VLP platform offers a safe, scalable, and immunologically optimized approach for MERS-CoV vaccine development.
• Further studies are warranted to confirm the protective potential in dromedaries and humans.