Neutralization of MERS 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 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 (mCuMVTT-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. mCuMVTT-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.

A scalable and highly immunogenic virus‐like particle‐based vaccine against SARS‐CoV‐2

“…Using this technique, we have recently developed a vaccine against MERS‐CoV by incorporating the RBM of MERS‐CoV into CuMV TT . The developed vaccine‐induced antibodies that completely neutralized MERS‐CoV/EMC/2012 isolate 46 . Furthermore, we have shown that fusing RBM into AP205‐VLPs results in an effective vaccine candidate which induced RBD‐ and spike‐specific antibodies which were capable of neutralizing the wild‐type virus SARS‐CoV‐2/ABS/NL20 35 .…”

Biological Nanoparticles in Vaccine Development

“…VLPs also contain viral PAMPs, such as nucleic acids, that help activate, in many cases, and an adjuvant-free protective immune response ( Venter et al, 2011 ; Li M. et al, 2021 ; Ortega-Rivera et al, 2021 ; Royal et al, 2021 ; Warner and Frietze, 2021 ). Additionally, if they are made in bacteria, VLPs may contain some bacterial components that further promote a protective response without use of classical alum adjuvants ( Mohsen et al, 2021 , 2022 ). As OMVs are directly derived from bacteria, they display many PAMPs that VLPs do not contain, such as LPS, flagellin, and lipopeptides, and making them self-adjuvanting.…”

“…This effect, despite being T cell-independent, then leads to strong stimulation of B cells and induction of a robust and long-lasting antibody response ( Bachmann et al, 1993 ; Fries et al, 2021 ) that can even be achieved without the addition of synthetic adjuvants ( Zhang et al, 2000 ; Li Y. et al, 2021 ). Furthermore, VLPs naturally encapsulate bacterial nucleic acids when propagated in bacterial expression systems, which further activate antigen-presenting cells and B cells ( Mohsen et al, 2021 ). The success of the VLP platform has already resulted in many FDA-approved VLP-based vaccines, including Cervarix ® ( Harper et al, 2004 ) and Gardasil ® ( Villa et al, 2005 ) for Human Papilloma Virus (HPV), and Engerix ® ( Keating et al, 2003 ) and Recombivax ® ( Van Damme et al, 2009 ) for Hepatitis B Virus (HBV) (see Table 1 ).…”

“…Chimeric viruses contain genetic material from two different viruses, which results in fusion proteins that incorporate epitopes from both viruses. Recombinant chimeric VLP vaccines have been developed for Chikungunya virus (CHIKV), based on the insect-specific alphavirus, Eilat virus (EILV) ( Erasmus et al, 2017 ); Bacillus anthracis , based on cowpea mosaic virus (CPMV) ( Phelps et al, 2007 ) and Flock house virus ( Venter et al, 2011 ); SARS-CoV-2 and MERS, based on cucumber mosaic virus (CMV) ( Mohsen et al, 2021 , 2022 ); and SARS-CoV-2 and Yersinia pestis , based on tobacco mosaic virus (TMV) ( Arnaboldi et al, 2016 ; Royal et al, 2021 ).…”

Induction of Broadly Cross-Reactive Antibodies by Displaying Receptor Binding Domains of SARS-CoV-2 on Virus-like Particles

“…For example, CuMV TT -Ara h 1 was demonstrated to effectively treat peanut allergy in mice [17]. Another example of CuMV TT as an excellent vaccine delivery vehicle was against MERS coronavirus, which was potent to induce high titers of RBD-and spike protein-specific IgG antibodies, which could neutralize virus in vitro [18].…”