Abstract

COVID-19 is a novel disease caused by SARS-CoV-2 which has conquered the world rapidly resulting in a pandemic that massively impacts our health, social activities, and economy. It is likely that vaccination is the only way to form “herd immunity” and restore the world to normal. Here we developed a vaccine candidate for COVID-19 based on the virus-like particle AP205 displaying the spike receptor binding motif (RBM), which is the major target of neutralizing antibodies in convalescent patients. To this end, we genetically fused the RBM domain of SARS-CoV-2 to the C terminus of AP205 of dimerized capsid proteins. The fused VLPs were expressed in E. coli, which resulted in insoluble aggregates. These aggregates were denatured in 8 M urea followed by refolding, which reconstituted VLP formation as confirmed by electron microscopy analysis. Importantly, immunized mice were able to generate high levels of IgG antibodies recognizing eukaryotically expressed receptor binding domain (RBD) as well as spike protein of SARS-CoV-2. Furthermore, induced antibodies were able to neutralize SARS-CoV-2/ABS/NL20. Additionally, this vaccine candidate has the potential to be produced at large scale for immunization programs.

Highlights

  • Introduction published maps and institutional affilThe current global pandemic of COVID-19 caused by the new coronavirus SARSCoV-2 has a large impact on the economic and social life worldwide

  • We have provided a proof-of-concept that AP205-Virus-like particles (VLPs) constitute an efficient vaccine platform that is suitable for fusing epitopes of different lengths such as peptides from angiotensin II, CXCR4 receptor, influenza A M2 protein or gonadotropin releasing hormone (GnRH)

  • Our first attempt to generate a COVID-19 vaccine was based on producing a recombiOur first attempt to generate a COVID-19 vaccine was based on producing a recomnant receptor binding domain (RBD) in human eukaryotic cells and chemically coupling the domain to CuMVTT -VLPs, binant RBD in human eukaryotic cells and chemically coupling the domain to CuMVTTresulting in a vaccine candidate that binds to ACE2 and induces neutralizing antibodies

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Summary

Introduction

Introduction published maps and institutional affilThe current global pandemic of COVID-19 caused by the new coronavirus SARSCoV-2 has a large impact on the economic and social life worldwide. Similar to the disease caused by the other two viruses SARS (SARS-CoV) and MERS (MERSCoV), COVID-19 leads to systemic infection and may cause organ failure, of the lung [1]. In contrast to SARS-CoV and MERS-CoV, which could be contained more efficiently, SARS-CoV-2 spreads more rapidly because of infected asymptomatic individuals (mostly pre-symptomatic) who can transmit the virus [2]. Many investigations aim at defining optimal strategies to limit viral transmission while simultaneously permitting business and social life activities [5]. One of these strategies is to rapidly increase the iations

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